Nengbo Lin, Hua Lu, Xiaoling Cheng, Ya Zhao, Qin Wan, Yi Luo, Ying Miao, Xue Bai, Dan Liu, Chao Wang
Diabetic retinopathy (DR) is a common microvascular complication of diabetes and the leading cause of blindness at working age. DR is considered to be a chronic low-grade inflammatory subclinical disease, and its pathogenesis is related to genetic and environmental factors. Interleukin (IL)-1 is an important inflammatory cytokine. An association between DR and the rs16944 (IL-1B-511) T>C gene polymorphism has not been reported. The aim of this study was to investigate the association between the rs16944 T>C gene polymorphism and DR in the Han population in southwest China. Participants in this study were 272 patients with DR, 274 patients with type 2 diabetes mellitus (T2DM), and 335 healthy controls (NC). The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the rs16944 T>C genotype of participants. The distribution frequencies of the rs16944 T>C genotype and allele were significantly different among the three groups (p < .05). The distribution frequency of TT, CT, CC genotype (χ2 = 9.893, p = .007; χ2 = 6.567, p = .037) and each allele (χ2 = 5.585, p = .018; χ2 = 9.187, p = .002) in the DR group was significantly different from the NC and T2DM groups, respectively. Logistic regression analysis showed that the TT + CT genotype was a risk factor for DR, with an odds ratio of 1.731 (95% confidence interval 1.140–2.627, p = .01). The rs16944 T>C gene polymorphism may be associated with DR, and the TT+CT genotype may increase the risk of DR.
糖尿病视网膜病变(DR)是糖尿病常见的微血管并发症，也是导致工作年龄失明的主要原因。DR被认为是一种慢性低度炎性亚临床疾病，其发病机制与遗传和环境因素有关。白细胞介素-1是一种重要的炎症细胞因子。DR与rs16944 (IL-1B-511) T>C基因多态性之间的关联尚未报道。本研究旨在探讨中国西南汉族人群rs16944 T>C基因多态性与DR的关系。本研究的参与者是272例DR患者，274例2型糖尿病(T2DM)患者和335名健康对照(NC)。采用聚合酶链反应-限制性片段长度多态性法检测受试者rs16944 T>C基因型。rs16944 T>C基因型和等位基因的分布频率在三组间差异有统计学意义(p <. 05)。TT、CT、CC基因型分布频率(χ2 = 9.893, p = 0.007;χ2 = 6.567, p = 0.037)，各等位基因差异有统计学意义(χ2 = 5.585, p = 0.018;χ2 = 9.187, p = 0.002)，与NC、T2DM组比较，差异均有统计学意义。Logistic回归分析显示，TT + CT基因型是发生DR的危险因素，比值比为1.731(95%可信区间1.140 ~ 2.627,p = 0.01)。rs16944 T>C基因多态性可能与DR相关，TT+CT基因型可能增加DR的风险。
{"title":"Association between the interleukin-1B polymorphism at rs16944 T>C and diabetic retinopathy","authors":"Nengbo Lin, Hua Lu, Xiaoling Cheng, Ya Zhao, Qin Wan, Yi Luo, Ying Miao, Xue Bai, Dan Liu, Chao Wang","doi":"10.1111/iji.12604","DOIUrl":"10.1111/iji.12604","url":null,"abstract":"<p>Diabetic retinopathy (DR) is a common microvascular complication of diabetes and the leading cause of blindness at working age. DR is considered to be a chronic low-grade inflammatory subclinical disease, and its pathogenesis is related to genetic and environmental factors. Interleukin (IL)-1 is an important inflammatory cytokine. An association between DR and the rs16944 (<i>IL-1B-511</i>) T>C gene polymorphism has not been reported. The aim of this study was to investigate the association between the rs16944 T>C gene polymorphism and DR in the Han population in southwest China. Participants in this study were 272 patients with DR, 274 patients with type 2 diabetes mellitus (T2DM), and 335 healthy controls (NC). The polymerase chain reaction-restriction fragment length polymorphism method was used to detect the rs16944 T>C genotype of participants. The distribution frequencies of the rs16944 T>C genotype and allele were significantly different among the three groups (<i>p</i> < .05). The distribution frequency of TT, CT, CC genotype (χ<sup>2</sup> = 9.893, <i>p</i> = .007; χ<sup>2</sup> = 6.567, <i>p</i> = .037) and each allele (χ<sup>2</sup> = 5.585, <i>p</i> = .018; χ<sup>2</sup> = 9.187, <i>p</i> = .002) in the DR group was significantly different from the NC and T2DM groups, respectively. Logistic regression analysis showed that the TT + CT genotype was a risk factor for DR, with an odds ratio of 1.731 (95% confidence interval 1.140–2.627, <i>p</i> = .01). The rs16944 T>C gene polymorphism may be associated with DR, and the TT+CT genotype may increase the risk of DR.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"50 1","pages":"34-40"},"PeriodicalIF":2.2,"publicationDate":"2022-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10556879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor β1 (IL-12Rβ2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rβ2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (p = .04, CI = 0.270–0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (p = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.
{"title":"Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients","authors":"Maryam Zare, Fatemeh Hesampour, Tahereh Poordast, Maryam Valibeigi, Maliheh Enayatmehri, Sahar Ahmadi, Fatemeh Nasri, Behrouz Gharesi-Fard","doi":"10.1111/iji.12606","DOIUrl":"10.1111/iji.12606","url":null,"abstract":"<p>Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor β1 (IL-12Rβ2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rβ2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (<i>p</i> = .04, CI = 0.270–0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (<i>p</i> = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"50 1","pages":"24-33"},"PeriodicalIF":2.2,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10491593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shrikant Verma, Sushma Verma, Faizan Haider Khan, Zeba Siddiqi, Syed Tasleem Raza, Mohammad Abbas, Farzana Mahdi
Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (–597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having ‘C’ allele of IL6 (–174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.
{"title":"Genetic polymorphisms of IL6 gene –174G > C and –597G > A are associated with the risk of COVID-19 severity","authors":"Shrikant Verma, Sushma Verma, Faizan Haider Khan, Zeba Siddiqi, Syed Tasleem Raza, Mohammad Abbas, Farzana Mahdi","doi":"10.1111/iji.12605","DOIUrl":"10.1111/iji.12605","url":null,"abstract":"<p>Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of <i>IL6</i> cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the <i>IL6</i> gene (–597G > A and –174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of <i>IL6</i> gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of <i>IL6</i> (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, <i>p</i> <.001] but we did not observe any association of COVID-19 severity with rs1800797 (–597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having ‘C’ allele of <i>IL6</i> (–174G > C) polymorphism (<i>p</i> = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (<i>p</i> = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of <i>IL6</i> may be the risk allele for severity of COVID-19 in North Indian population.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"50 1","pages":"5-11"},"PeriodicalIF":2.2,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878250/pdf/IJI-50-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The following sequences have been submitted to the Nomenclature Committee since the April, May and June 2022 nomenclature update (Marsh, 2022) and, following agreed policy, have been assigned official allele designations (Marsh et al., 2010). Full details of all sequenceswill be published in a forthcoming report. Below are listed the newly assigned sequences (Table 1) and confirmations of previously reported sequences (Table 2). The accession number of each sequence is given and these can be used to retrieve the sequence files from the EMBL, GenBank or DDBJ data libraries. Although accession numbers have been assigned by the data libraries and most sequences are already available, there is still the possibility that an author may not yet have allowed the sequence to be released; in such a case, you will have to contact the submitting author directly. Additional information pertaining to new sequences is often included in the publications describing these alleles; a listing of recent publications that describe new HLA sequences is given in Table 3.
{"title":"Nomenclature for factors of the HLA system, update July, August and September 2022","authors":"Steven G. E. Marsh","doi":"10.1111/iji.12603","DOIUrl":"10.1111/iji.12603","url":null,"abstract":"The following sequences have been submitted to the Nomenclature Committee since the April, May and June 2022 nomenclature update (Marsh, 2022) and, following agreed policy, have been assigned official allele designations (Marsh et al., 2010). Full details of all sequenceswill be published in a forthcoming report. Below are listed the newly assigned sequences (Table 1) and confirmations of previously reported sequences (Table 2). The accession number of each sequence is given and these can be used to retrieve the sequence files from the EMBL, GenBank or DDBJ data libraries. Although accession numbers have been assigned by the data libraries and most sequences are already available, there is still the possibility that an author may not yet have allowed the sequence to be released; in such a case, you will have to contact the submitting author directly. Additional information pertaining to new sequences is often included in the publications describing these alleles; a listing of recent publications that describe new HLA sequences is given in Table 3.","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 6","pages":"385-416"},"PeriodicalIF":2.2,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40676276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as DRB1 and DQB1 are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population. However, the genetic screening of HLA class II alleles and haplotypes in Pakistani asthmatics has not been studied so far. The aim of the present study was to screen the HLA class II DRB1 and DQB1 alleles in asthma cases and controls in a Pakistani population. Seven hundred and two healthy controls and asthma patients were genotyped for HLA class II by sequence-specific polymerase chain reaction assays. The HLA-DRB1 and HLA-DQB1 allele and haplotype frequencies were calculated, and their risk or protective association with asthma was determined. Two-locus haplotypes of DRB1 and DQB1 alleles were imputed using Arlequin version 3.1 software. The signals of association with asthma were stronger at the DQB1 locus as compared to DRB1. HLA DQB1*03:03:02 (odds ratio [OR] = 2.42, 95% confidence interval [CI] = 1.34–4.25) was significantly associated with an increased risk of asthma, as was the haplotype comprised allele DRB1*07:01-DQB1*03:03:02 (OR = 2.40, 95% CI = 1.25–4.62). In contrast, DQB1*06 (OR = 0.39, 95% CI = 0.22–0.70) and DQB1*06:02 (OR = 0.27, 95% CI = 0.10–0.71) emerged as protective alleles for asthma. Our data concludes that the HLA DQB1*03:03:02 allele was a risk allele for asthma, whereas two DQB1 alleles, DQB1*06 and DQB1*06:02, were associated with asthma protection. Our findings highlight a prominent role for HLA-DQB1 alleles in asthma pathogenesis in studied Pakistani cases. More studies, especially with a larger study cohort are needed to confirm the utility of HLA DQB1*03:03:02 as a predictive marker.
{"title":"Study of HLA class II loci reveals DQB1*03:03:02 as a risk factor for asthma in a Pakistani population","authors":"Nusrat Saba, Ghazala Kaukab Raja, Osman Yusuf, Sadia Rehman, Saeeda Munir, Sumaira Sajjad, Atika Mansoor","doi":"10.1111/iji.12602","DOIUrl":"10.1111/iji.12602","url":null,"abstract":"<p>Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as <i>DRB1</i> and <i>DQB1</i> are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population. However, the genetic screening of HLA class II alleles and haplotypes in Pakistani asthmatics has not been studied so far. The aim of the present study was to screen the HLA class II <i>DRB1</i> and <i>DQB1</i> alleles in asthma cases and controls in a Pakistani population. Seven hundred and two healthy controls and asthma patients were genotyped for HLA class II by sequence-specific polymerase chain reaction assays. The <i>HLA-DRB1</i> and <i>HLA-DQB1</i> allele and haplotype frequencies were calculated, and their risk or protective association with asthma was determined. Two-locus haplotypes of <i>DRB1</i> and <i>DQB1</i> alleles were imputed using Arlequin version 3.1 software. The signals of association with asthma were stronger at the DQB1 locus as compared to DRB1. <i>HLA DQB1*03:03:02</i> (odds ratio [OR] = 2.42, 95% confidence interval [CI] = 1.34–4.25) was significantly associated with an increased risk of asthma, as was the haplotype comprised allele <i>DRB1*07:01-DQB1*03:03:02</i> (OR = 2.40, 95% CI = 1.25–4.62). In contrast, <i>DQB1*06</i> (OR = 0.39, 95% CI = 0.22–0.70) and <i>DQB1*06:02</i> (OR = 0.27, 95% CI = 0.10–0.71) emerged as protective alleles for asthma. Our data concludes that the <i>HLA DQB1*03:03:02</i> allele was a risk allele for asthma, whereas two DQB1 alleles, <i>DQB1*06</i> and <i>DQB1*06:02</i>, were associated with asthma protection. Our findings highlight a prominent role for <i>HLA-DQB1</i> alleles in asthma pathogenesis in studied Pakistani cases. More studies, especially with a larger study cohort are needed to confirm the utility of <i>HLA DQB1*03:03:02</i> as a predictive marker.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 6","pages":"372-378"},"PeriodicalIF":2.2,"publicationDate":"2022-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stéphanie Gomes Santos de Almeida, Fabiana Batalha Knakcfuss, Lívia Maria Assis, Regina Celia Gonçalves de Sousa, Tereza Azevedo Matuck, Deise de Boni Monteiro de Carvalho, Ricardo Luiz Dantas Machado, Maria Angelica Arpon Marandino Guimarães, Rafael Brandão Varella
We investigated the effects of TNF-α, IFN-γ, IL-10 polymorphisms on viral infections (CMV, BKPyV, HHV-6, EBV) after renal transplantation. IFN-γ+874 A > T (lower IFN production) was associated with CMV disease (p = .039) in patients under mycophenolate-based therapy and graft failure (p = .025). This study underscores the role of IFN-γ+874 SNP in CMV infection.
{"title":"Investigation of cytokine polymorphisms on viral infections after renal transplantation exhibit association between IFN-γ +874 A > T and CMV manifestations","authors":"Stéphanie Gomes Santos de Almeida, Fabiana Batalha Knakcfuss, Lívia Maria Assis, Regina Celia Gonçalves de Sousa, Tereza Azevedo Matuck, Deise de Boni Monteiro de Carvalho, Ricardo Luiz Dantas Machado, Maria Angelica Arpon Marandino Guimarães, Rafael Brandão Varella","doi":"10.1111/iji.12601","DOIUrl":"10.1111/iji.12601","url":null,"abstract":"<p>We investigated the effects of TNF-α, IFN-γ, IL-10 polymorphisms on viral infections (CMV, BKPyV, HHV-6, EBV) after renal transplantation. IFN-γ+874 A > T (lower IFN production) was associated with CMV disease (<i>p</i> = .039) in patients under mycophenolate-based therapy and graft failure (<i>p</i> = .025). This study underscores the role of IFN-γ+874 SNP in CMV infection.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 6","pages":"379-383"},"PeriodicalIF":2.2,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33487594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><b><span>Christopher Byrnes</span></b><sup>1</sup>, Andrew Hastings<sup>2</sup>, Ira Lacej<sup>2</sup>, Renuka Palanicawandar<sup>2</sup>, Eduardo Olavarria<sup>2</sup>, Arthi Anand<sup>1</sup></p><p><i><sup>1</sup>Histocompatbility and Immunogenetics, North West London Pathology, London, UK; <sup>2</sup>Department of Haematology, Imperial College Healthcare NHS Trust, London, UK</i></p><p>Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells are the first to reconstitute post HSCT, suppressing graft versus host disease and mediating the graft versus leukaemia effect, driven by killer cell immunoglobulin-like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence outcomes of haploidentical HPCT. Haploidentical donors are readily available, and donor selection could hinge on predicted KIR NK cell alloreactivity. This study investigates whether donors with greater KIR B motifs associate with greater relapse free survival (RFS), overall survival (OS), non-relapse mortality (NRM), acute graft versus host disease (GvHD) and infection.</p><p>Following KIR genotyping, seventy-seven haploidentical donor recipient pairs (myeloablative <i>n</i> = 30, RIC <i>n</i> = 47) with various haematological malignancies are categorised into neutral (<i>n</i> = 49) or better and best (<i>n</i> = 28), using KIR B motif content. Kaplan-Meier and Cox Regression survival functions are performed to investigate associations with potential outcomes.</p><p>Our results show that the better and best category has significantly reduced RFS (<i>p</i> = .004) (HR 4.13, 95% CI 1.45–11.74: <i>p</i> = .008) and trend towards greater infections (<i>p</i> = .080) (HR 2.09, 95% CI 0.90–4.84: <i>p</i> < .1), decreasing OS (<i>p</i> = .008) (HR2.44, 95% confidence interval [CI] 1.24–4.81: <i>p</i> = .01), without impacting GvHD or NRM.</p><p>In our study, neutral donor outcomes are favourable in T cell depleted haplo-HPCT, potentially due to alloresponsive donor NK cells being targeted by immunosuppressive PTCy treatment delaying reconstitution. Further studies focusing on a homogenous pathology and treatment modality would determine the utility of KIR B content calculator in haploidentical donor selection.</p><p><b><span>Miss Rebecca Cope</span></b><sup>1,2</sup>, Rhea McArdle<sup>1,2</sup>, Veena Surendrakumar<sup>3</sup>, Afzal Chaudhry<sup>1,4</sup>, Vasilis Kosmoliaptsis<sup>3</sup>, Gavin Pettigrew<sup>3</sup>, Stephen Pettit<sup>5</sup>, Peter Riddle<sup>5</sup>, Sarah Peacock<sup>1</sup></p><p><i><sup>1</sup>Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; <sup>2</sup>Faculty of Biology, Medicine and Health, Division of Medical Education, School of Medical Sciences, The University of Manchester, Manchester, UK; <sup>3</sup>Department of Surgery, University of Cambridge, Cambridge, UK; <sup>4</sup>Department of Medici
{"title":"Oral Abstract","authors":"","doi":"10.1111/iji.12587","DOIUrl":"10.1111/iji.12587","url":null,"abstract":"<p><b><span>Christopher Byrnes</span></b><sup>1</sup>, Andrew Hastings<sup>2</sup>, Ira Lacej<sup>2</sup>, Renuka Palanicawandar<sup>2</sup>, Eduardo Olavarria<sup>2</sup>, Arthi Anand<sup>1</sup></p><p><i><sup>1</sup>Histocompatbility and Immunogenetics, North West London Pathology, London, UK; <sup>2</sup>Department of Haematology, Imperial College Healthcare NHS Trust, London, UK</i></p><p>Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells are the first to reconstitute post HSCT, suppressing graft versus host disease and mediating the graft versus leukaemia effect, driven by killer cell immunoglobulin-like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence outcomes of haploidentical HPCT. Haploidentical donors are readily available, and donor selection could hinge on predicted KIR NK cell alloreactivity. This study investigates whether donors with greater KIR B motifs associate with greater relapse free survival (RFS), overall survival (OS), non-relapse mortality (NRM), acute graft versus host disease (GvHD) and infection.</p><p>Following KIR genotyping, seventy-seven haploidentical donor recipient pairs (myeloablative <i>n</i> = 30, RIC <i>n</i> = 47) with various haematological malignancies are categorised into neutral (<i>n</i> = 49) or better and best (<i>n</i> = 28), using KIR B motif content. Kaplan-Meier and Cox Regression survival functions are performed to investigate associations with potential outcomes.</p><p>Our results show that the better and best category has significantly reduced RFS (<i>p</i> = .004) (HR 4.13, 95% CI 1.45–11.74: <i>p</i> = .008) and trend towards greater infections (<i>p</i> = .080) (HR 2.09, 95% CI 0.90–4.84: <i>p</i> < .1), decreasing OS (<i>p</i> = .008) (HR2.44, 95% confidence interval [CI] 1.24–4.81: <i>p</i> = .01), without impacting GvHD or NRM.</p><p>In our study, neutral donor outcomes are favourable in T cell depleted haplo-HPCT, potentially due to alloresponsive donor NK cells being targeted by immunosuppressive PTCy treatment delaying reconstitution. Further studies focusing on a homogenous pathology and treatment modality would determine the utility of KIR B content calculator in haploidentical donor selection.</p><p><b><span>Miss Rebecca Cope</span></b><sup>1,2</sup>, Rhea McArdle<sup>1,2</sup>, Veena Surendrakumar<sup>3</sup>, Afzal Chaudhry<sup>1,4</sup>, Vasilis Kosmoliaptsis<sup>3</sup>, Gavin Pettigrew<sup>3</sup>, Stephen Pettit<sup>5</sup>, Peter Riddle<sup>5</sup>, Sarah Peacock<sup>1</sup></p><p><i><sup>1</sup>Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; <sup>2</sup>Faculty of Biology, Medicine and Health, Division of Medical Education, School of Medical Sciences, The University of Manchester, Manchester, UK; <sup>3</sup>Department of Surgery, University of Cambridge, Cambridge, UK; <sup>4</sup>Department of Medici","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 S1","pages":"3-9"},"PeriodicalIF":2.2,"publicationDate":"2022-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49143208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><b><span>Anthony Calvert</span></b><sup>1</sup>, Anthony Poles<sup>1</sup>, Matthew Hopkins<sup>1</sup>, Tim Hayes<sup>2</sup></p><p><i><sup>1</sup>NHS Blood and Transplant, Filton, UK; <sup>2</sup>Manchester University NHS Foundation Trust, UK</i></p><p>Heparin induced thrombocytopenia (HIT) is a rare complication of heparin therapy with mild thrombocytopenia but potentially fatal thrombosis. HIT antibodies target the epitope of platelet factor 4 (PF4) and heparin. Laboratory investigations commonly detect antibodies by ELISA. The British Society for Haematology guidelines suggest clinical significant IgG antibodies equate to an OD > 1.0. Studies show an OD ≥ 1.4 corresponds with ≥50% chance of positive serotonin release assay (SRA) (Warkentin et al. J Thromb Haemost 2008; 6(8):1304-12).</p><p>Common practice for a HIT positive patient is repeat testing until a negative result indicates the safe use of Heparin, which is then administered pre-procedure and ceased immediately afterwards. Conditioning includes antibody titre reduction by plasmapheresis, multiple sessions are costly and can delay surgery. PF4/heparin antibodies are detected in 5-22% cardiac surgery patients but only 1%–2% have HIT (Pishko et al. Semin Thromb Hemost 2017; 43(7): 691-698).</p><p>A HIT positive pre-transplant patient was tested after each plasmapheresis using ELISA (Immucor HAT45G) and a platelet activation assay (IQ Products HITAlert) to compare HIT antibody levels with ability to activate platelets. Results showed an OD > 1.4 associated with positive activation, comparable to Warkentin's observations. The advantage of HITAlert is it detects functional antibodies and measures the expression of activation markers by flow cytometry, not radiolabelled serotonin release. The assay is then suitable for use in the routine laboratory environment, but requires freshly isolated (<2 h) ABO O platelets.</p><p>The patient received a successful heart transplant after the first negative activation result, sooner than waiting for negative ELISA results.</p><p><b><span>Carla Rosser</span></b><sup>1</sup>, Deborah Sage<sup>1</sup></p><p><i><sup>1</sup>NHS Blood and Transplant, Tooting, UK</i></p><p>The use of antibody-epitope analysis tools can improve the interpretation of in vitro HLA antibody identification assay data, particularly for identification of false positive reactions. HLA antibody-epitope analysis using HLAMatchmaker was performed on 22 crossmatched sera where donor-specific antibody (DSA) had previously been identified by One Lambda LABScreen™ Single Antigen (LABScreen). These sera were retrospectively tested by Immucor LIFECODES LSA (LIFECODES) and BAG Healthcare HISTO SPOT® (HISTO SPOT) assays.</p><p>All three HLA antibody identification assays identified DSA in serum that did not cause a positive flow-cytometric crossmatch (FCXM). Antibody-epitope analysis supports the presence of DSA in 12/22 of these sera, indicating a higher sensitivity of the solid ph
在这里，我们描述了移植后HLA分型对治疗选择产生重大影响的两个病例。两名患者在接受单倍体兄弟姐妹移植后都经历了复发。在复发诊断时进行NGS HLA分型，这些结果与移植后嵌合和细胞遗传学检测相结合，证实一名患者经历HLA丢失，而另一名患者没有。因此，复发并HLA丢失的患者继续进行第二次单倍体移植，而未HLA丢失的复发患者则考虑进行DLI移植。Anna Barker1, Laura Ford1, Stephine Whiteside1, Poppy Greenaway1, Rebecca Dench1, Helena lee11曼彻斯特大学NHS基金会信托基金，曼彻斯特，英国，用于干细胞移植后植入监测的谱系特异性嵌合分析已大大增加;在过去的两年里增长了51%。血样处理需要在采集后24小时内完成，因此在星期五收到的血样必须在当天处理。将细胞分离时间延长至24小时以上作为实验室工作流程审查的一部分进行了研究，目的是减少工作人员时间和仪器的压力。使用RoboSep™-S (STEMCELL™Technologies)自动细胞分离器从血液中分离CD3+和CD15+细胞。4名患者的样本分别在3个时间点进行处理(样本1 - 3在1、3和5天，样本4在3、6和7天)。提取的DNA使用GenePrint®24系统(Promega)进行常规嵌合检测。用流式细胞术测定每个分离细胞群的纯度。样品放置5天(有一例7天)对细胞群纯度、供体嵌合率(表1)和电泳峰高(均为>3000 RFU)。虽然最好立即处理样品，但工作量往往超过仪器容量和处理样品的可用时间。结果的质量在5天内不受影响，这意味着周五晚收到的样品可以在周一处理，减少了工作人员的时间压力。伊娃·桑托斯-努内兹1，卡特里娜·斯宾斯利2，科琳娜·弗里曼3，米歇尔·威利科姆2，阿蒂·阿南德1实验室哈默史密斯医院，伦敦西北部病理由帝国理工学院NHS信托主办，英国伦敦;2西伦敦肾移植中心，帝国学院NHS信托，伦敦，英国;使用算法计算分子错配需要高分辨率或第二场(2F)的HLA分型。然而，这种级别的分辨率并不总是可用的。为了克服这个问题，可以使用计算机算法来推断第二场基因型。目的:确定使用2F预测算法Easy-HLA (https://hla.univ-nantes.fr/recherche/recherche.php)的准确性，以及结果的差异是否会导致两种表位分析工具的分子错配评分的差异。方法:将28例肾移植受者用PCR-SSO (n = 23)和PCR-SSP (n = 5)生成的HLA类型上传到Easy-HLA的“HLA- upgrade tool”中。用NGS对样品重新分型，并对结果进行比较。采用HLAMatchmaker (www.epitopes.net)和PIRCHE-II算法(www.pirche.com)计算HLA等位基因错配负荷和PIRCHE-II评分。结果:单点单点升级(E-SSO)估计的每个位点2F等位基因的准确率分别为HLA- a(93.5%)、HLA- b(95.7%)、HLA- c(93.5%)、HLA- drb1(91.3%)、HLA- dqb1(97.8%)，单点单点升级(E-SSP)估计的准确率分别为80.0%、80.0%、80.0%、60.0%和40.0%。种族准确度的差异也被注意到;白(97.5%)、黑(94.4%)、亚洲(91.2%),其他(90.0%)。HLA Matchmaker对I类和II类的E-SSO一致性分别为96%和100%，对E-SSP的一致性分别为60%和40%。在7/23(30%)的E-SSO样本(范围0-62)和3/5(60%)的E-SSP样本(范围0-95)中，PIRCHE II评分出现偏差。结论:总之，从中级分型中成功推断出2F数据是可能的。利用Easy-HLA等算法提供的中间(SSO)分型结果和统计及群体遗传学数据可以提高准确率。Emma Holmes1, Jennifer gas1, Sue Jordan1, Deborah Sage11NHS血液与移植中心，图汀，英国虚拟交叉配型广泛用于评估肾移植受者和已故供者之间的相容性，以减少冷缺血时间。在图廷的NHS血液和移植中心，只有HLA抗体阴性且之前没有移植过的患者才有资格进行虚拟交叉配型。分析了2016年至2020年进行的735例死亡供体交叉配型，其中494例患者进行了移植，以确定是否可以将合格标准扩展到包括HLA抗体阳性的患者，这些患者没有针对潜在供体的供体特异性抗体(DSA)。 HLA抗体阴性患者5202例(68%)进行交叉配型，其中虚拟交叉配型383例。在没有DSA的情况下，HLA抗体阳性患者进行了127例(17%)实验室交叉配型。根据BSHI/BTS指南，所有这些都被报告为具有标准的免疫风险，这表明实验室交叉配型除了HLA抗体检测外，没有提供可能改变临床患者管理的额外信息。有DSA存在的HLA抗体阳性患者进行了106例(14%)实验室交叉配型。这三组患者中都包括之前接受过移植的患者。NHSBT-OTDT报告的临床排斥事件分析显示，三组患者的急性排斥发生率相似。根据这些数据，虚拟交叉匹配策略已扩展到包括无DSA的敏感患者。HLA抗体检测用于确认患者的抗体谱在移植时保持不变。Jennifer gas1, Susan Jordan1, Deborah Sage11NHSBT, London, uk1肾移植受者HLA抗体的特征对于评估其与潜在的已故或活体供者的相容性是必要的。单抗原珠(SAB)固相测定法简化了抗体分析，然而，通过抗原靶来定义这些抗体，而不是通过抗原靶来定义这些抗体，被认为更具临床相关性。在本病例研究中，我们报告了一位46岁的男性肾脏移植患者，我们使用One Lambda Labscreen SAB试验对其血清进行了检测，发现其血清中含有针对HLA-DP的抗体，该抗体不能单独由DPB1或DPA1靶点定义。结合表位注册表和公开的晶体结构，确定DPA1位置50(谷氨酰胺，Q或精氨酸，R)和DPB1位置85-87(谷氨酸-丙氨酸-缬氨酸(EAV)或甘氨酸-脯氨酸-蛋氨酸(GPM))可以构成单一抗体靶点。重新分析该患者的SAB谱显示，只有上述位置的Q和EAV的DP抗原呈阳性。NGS HLA-DP分型显示为Q-GPM。进一步使用Immucor Lifecodes单抗原试剂盒和Labscreen Supplementary Class II SAB试剂盒进行HLA抗体检测也得到了DP抗体谱，这可以用Q-EAV表位靶点来解释。该患者抗体仅在与携带Q-EAV DP分子的细胞孵育时发生吸收;Q-GPM无吸收。将可能结合的α - β链表位纳入表位分析软件，并列出表位，而不是抗原，作为不可接受的，将为未来的兼容性评估提供更有针对性的方法。Sejal morjari1, Arun Gupta1, Delordson M kallon11临床移植实验室，Barts Health NHS Trust, London, uk胸腺移植是一种新兴的临床选择，用于出生时没有胸腺的婴儿，这是一种与迪乔治综合征(DGS)相关的症状。患者AN(3个月，女性)于201
{"title":"Poster Abstract","authors":"","doi":"10.1111/iji.12586","DOIUrl":"10.1111/iji.12586","url":null,"abstract":"<p><b><span>Anthony Calvert</span></b><sup>1</sup>, Anthony Poles<sup>1</sup>, Matthew Hopkins<sup>1</sup>, Tim Hayes<sup>2</sup></p><p><i><sup>1</sup>NHS Blood and Transplant, Filton, UK; <sup>2</sup>Manchester University NHS Foundation Trust, UK</i></p><p>Heparin induced thrombocytopenia (HIT) is a rare complication of heparin therapy with mild thrombocytopenia but potentially fatal thrombosis. HIT antibodies target the epitope of platelet factor 4 (PF4) and heparin. Laboratory investigations commonly detect antibodies by ELISA. The British Society for Haematology guidelines suggest clinical significant IgG antibodies equate to an OD > 1.0. Studies show an OD ≥ 1.4 corresponds with ≥50% chance of positive serotonin release assay (SRA) (Warkentin et al. J Thromb Haemost 2008; 6(8):1304-12).</p><p>Common practice for a HIT positive patient is repeat testing until a negative result indicates the safe use of Heparin, which is then administered pre-procedure and ceased immediately afterwards. Conditioning includes antibody titre reduction by plasmapheresis, multiple sessions are costly and can delay surgery. PF4/heparin antibodies are detected in 5-22% cardiac surgery patients but only 1%–2% have HIT (Pishko et al. Semin Thromb Hemost 2017; 43(7): 691-698).</p><p>A HIT positive pre-transplant patient was tested after each plasmapheresis using ELISA (Immucor HAT45G) and a platelet activation assay (IQ Products HITAlert) to compare HIT antibody levels with ability to activate platelets. Results showed an OD > 1.4 associated with positive activation, comparable to Warkentin's observations. The advantage of HITAlert is it detects functional antibodies and measures the expression of activation markers by flow cytometry, not radiolabelled serotonin release. The assay is then suitable for use in the routine laboratory environment, but requires freshly isolated (<2 h) ABO O platelets.</p><p>The patient received a successful heart transplant after the first negative activation result, sooner than waiting for negative ELISA results.</p><p><b><span>Carla Rosser</span></b><sup>1</sup>, Deborah Sage<sup>1</sup></p><p><i><sup>1</sup>NHS Blood and Transplant, Tooting, UK</i></p><p>The use of antibody-epitope analysis tools can improve the interpretation of in vitro HLA antibody identification assay data, particularly for identification of false positive reactions. HLA antibody-epitope analysis using HLAMatchmaker was performed on 22 crossmatched sera where donor-specific antibody (DSA) had previously been identified by One Lambda LABScreen™ Single Antigen (LABScreen). These sera were retrospectively tested by Immucor LIFECODES LSA (LIFECODES) and BAG Healthcare HISTO SPOT® (HISTO SPOT) assays.</p><p>All three HLA antibody identification assays identified DSA in serum that did not cause a positive flow-cytometric crossmatch (FCXM). Antibody-epitope analysis supports the presence of DSA in 12/22 of these sera, indicating a higher sensitivity of the solid ph","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 S1","pages":"10-20"},"PeriodicalIF":2.2,"publicationDate":"2022-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62685207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ewa Paszkiewicz-Kozik, Anna Kluska, Magdalena Piątkowska, Aneta Bałabas, Natalia Żeber-Lubecka, Jakub Karczmarski, Krzysztof Goryca, Maria Kulecka, Elżbieta Wojciechowska-Lampka, Włodzimierz Osiadacz, Joanna Romejko-Jarosińska, Monika Świerkowska, Agnieszka Paziewska, Filip Ambrożkiewicz, Jan Walewski, Michał Mikula, Jerzy Ostrowski
Several single nucleotide polymorphisms (SNPs) associated with susceptibility to Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have been identified. The aim of this study was to identify susceptibility loci for HL and DLBCL in Polish patients. Altogether, DLBCL (n = 218 and HL patients (n = 224) and healthy individuals (n = 1181) were recruited. Lymphoma diagnosis was based on standard criteria. Genome-wide association study (GWAS) was performed using pooled-DNA samples on llumina Infinium Omni2.5 Exome-8 v1.3, and selected loci were replicated by TaqMan SNP genotyping of individuals. GWAS detected thirteen and seven SNPs associated with DLBCL and HL, respectively. In the replication study, six and seven SNPs reached significance after correction for multiple testing in the DLBCL and HL cohorts, respectively. One and four SNPs associated with DLBCL and HL, respectively, were localized within, and two SNPs—near the major histocompatibility complex (MHC) region. In conclusion, the majority of loci associated with HL and DLBCL aetiology in previous studies have potential roles in immune function. Our pooled-DNA GWAS enabled the identification of several susceptibility loci for DLBCL and HL in the Polish population; some of them were mapped within or adjacent to the MHC, and other associated SNPs were located outside the MHC.
{"title":"Genetic associations with lymphomas in Polish patients: A pooled-DNA genome-wide association analysis","authors":"Ewa Paszkiewicz-Kozik, Anna Kluska, Magdalena Piątkowska, Aneta Bałabas, Natalia Żeber-Lubecka, Jakub Karczmarski, Krzysztof Goryca, Maria Kulecka, Elżbieta Wojciechowska-Lampka, Włodzimierz Osiadacz, Joanna Romejko-Jarosińska, Monika Świerkowska, Agnieszka Paziewska, Filip Ambrożkiewicz, Jan Walewski, Michał Mikula, Jerzy Ostrowski","doi":"10.1111/iji.12596","DOIUrl":"10.1111/iji.12596","url":null,"abstract":"<p>Several single nucleotide polymorphisms (SNPs) associated with susceptibility to Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have been identified. The aim of this study was to identify susceptibility loci for HL and DLBCL in Polish patients. Altogether, DLBCL (<i>n</i> = 218 and HL patients (<i>n</i> = 224) and healthy individuals (<i>n</i> = 1181) were recruited. Lymphoma diagnosis was based on standard criteria. Genome-wide association study (GWAS) was performed using pooled-DNA samples on llumina Infinium Omni2.5 Exome-8 v1.3, and selected loci were replicated by TaqMan SNP genotyping of individuals. GWAS detected thirteen and seven SNPs associated with DLBCL and HL, respectively. In the replication study, six and seven SNPs reached significance after correction for multiple testing in the DLBCL and HL cohorts, respectively. One and four SNPs associated with DLBCL and HL, respectively, were localized within, and two SNPs—near the major histocompatibility complex (MHC) region. In conclusion, the majority of loci associated with HL and DLBCL aetiology in previous studies have potential roles in immune function. Our pooled-DNA GWAS enabled the identification of several susceptibility loci for DLBCL and HL in the Polish population; some of them were mapped within or adjacent to the MHC, and other associated SNPs were located outside the MHC.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 5","pages":"353-363"},"PeriodicalIF":2.2,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33445118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We aimed to determine whether the interferon (IFN)-γ +874 T/A polymorphism (rs2430561) is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to assess the association between the IFN-γ +874 T/A polymorphism and SLE or RA using allele contrast, homozygous contrast, recessive, and dominant models. A total of nine studies (six on SLE and three on RA), involving 1839 patients and 2272 controls, were included in the meta-analysis. The meta-analysis revealed a significant association between SLE and the TT genotype of the IFN-γ +874 T/A polymorphism (odds ratio [OR] = 0.751, 95% confidence interval [CI] = 0.634–0.899, p = .001), and stratification by ethnicity indicated an association between the IFN-γ +874 TT genotype and the Asian population. The analysis also revealed a significant association between SLE and the TT + TA genotype of the IFN-γ +874 T/A polymorphism in Arab populations (OR = 1.598, 95% CI = 1.053–2.425, p = .028). However, no association between the IFN-γ +874 T/A polymorphism and RA was found using allele contrast, recessive, dominant or homozygous contrast models in all study subjects and ethnic groups. This meta-analysis demonstrated that the IFN-γ +874 T/A polymorphism is associated with susceptibility to SLE in Asian and Arab populations.
{"title":"Association between the interferon-γ +874 T/A polymorphism and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: A meta-analysis","authors":"Young Ho Lee, Gwan Gyu Song","doi":"10.1111/iji.12599","DOIUrl":"10.1111/iji.12599","url":null,"abstract":"<p>We aimed to determine whether the interferon (IFN)<i>-γ</i> +874 T/A polymorphism (rs2430561) is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to assess the association between the IFN<i>-γ</i> +874 T/A polymorphism and SLE or RA using allele contrast, homozygous contrast, recessive, and dominant models. A total of nine studies (six on SLE and three on RA), involving 1839 patients and 2272 controls, were included in the meta-analysis. The meta-analysis revealed a significant association between SLE and the TT genotype of the IFN<i>-γ</i> +874 T/A polymorphism (odds ratio [OR] = 0.751, 95% confidence interval [CI] = 0.634–0.899, <i>p</i> = .001), and stratification by ethnicity indicated an association between the IFN<i>-γ</i> +874 TT genotype and the Asian population. The analysis also revealed a significant association between SLE and the TT + TA genotype of the IFN<i>-γ</i> +874 T/A polymorphism in Arab populations (OR = 1.598, 95% CI = 1.053–2.425, <i>p</i> = .028). However, no association between the IFN<i>-γ</i> +874 T/A polymorphism and RA was found using allele contrast, recessive, dominant or homozygous contrast models in all study subjects and ethnic groups. This meta-analysis demonstrated that the IFN<i>-γ</i> +874 T/A polymorphism is associated with susceptibility to SLE in Asian and Arab populations.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"49 6","pages":"365-371"},"PeriodicalIF":2.2,"publicationDate":"2022-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33441676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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