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.
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.
Human neutrophil antigens possess significant clinical implications especially in the fields of transfusion and transplantation medicine. Efforts to estimate the prevalence of genetic variations underpinning the antigenic expression are emerging. However, there lacks a precise capture of the global frequency profiles. Our article emphasizes the potential utility of maintaining an organized online repository of evidence on neutrophil antigen-associated genetic variants from published literature and reports. This, in our opinion, is an emerging area and would significantly benefit from the awareness and understanding of population-level diversities.
Host genetic factors may be correlated with the severity of coronavirus disease 2019 (COVID-19). Angiotensin-converting enzyme 2 (ACE2) plays a vital role in viral cell entrance. The current study aimed to evaluate the association of ACE2 rs2285666 polymorphism and clinical parameters with COVID-19 mortality. The ACE2 rs2285666 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism in 556 recovered and 522 dead patients. In this study, the frequency of ACE2 rs2285666 CC was significantly higher than TT genotype in dead patients. The multivariate logistic regression analysis results showed that the higher levels of alanine aminotransferase, alkaline phosphatase, creatinine, erythrocyte sedimentation rate, and C-reactive protein and the low levels of uric acid, cholesterol, low density lipoprotein, 25-hydroxyvitamin D, real-time PCR Ct values, and ACE2 rs2285666 CC genotype were associated with increased mortality rates after COVID-19. In conclusion, our findings demonstrated a possible link between COVID-19 mortality, clinical parameters, and ACE2 rs2285666 CC. Further research is required to confirm these results.
The HISTO SPOT®AB ID assay (BAG Diagnostics GmbH) is a novel single antigen HLA Class I & II antibody definition test used with the MR.SPOT® processor. We compared this assay with Luminex®-based assays to assess its potential application in defining unacceptable antigens for transplantation in patients awaiting transplants with cardiothoracic organs. A cohort of 40 sensitized cardiothoracic patients were identified, and one sample was selected from each patient. The required screening was based on the patients’ antibody profiles (Class I, n = 17, Class II, n = 11, Class I & II, n = 12). Samples were screened with LABScreen™ Single Antigen (SAg), LIFECODES® LSA™, HISTO SPOT® AB ID, and an acid modified LABScreen™ SAg test for detecting antibodies against denatured HLA. Results indicated that HISTO SPOT® AB ID had reduced sensitivity (68% for Class I; 69% for Class II). When compared to LABScreen™ and LIFECODES®, HISTO SPOT® AB ID failed to detect Luminex®-defined antibodies with median fluorescence intensity (MFI) ranging from 1114 to 24,489. The HISTO SPOT® AB ID panel used in the study had reduced antigen representation compared with Luminex®-based assays which further compromised its capacity for antibody detection and definition. Further work is needed to evaluate the clinical relevance of these differences between the performance of HISTO SPOT® and Luminex®-based methods.
Multiple sclerosis (MS) is a chronic neurological disease believed to be caused by autoimmune pathogenesis. The aetiology is likely explained by a complex interplay between inherited and environmental factors. Genetic investigations into MS have been conducted for over 50 years, yielding >100 associations to date. Globally, the strongest linkage is with the human leukocyte antigen (HLA) HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype.
Here, high-resolution sequencing of HLA was used to determine the alleles of DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1 and DPB1 as well as their extended haplotypes and genotypes in 100 Swedish MS patients. Results were compared to 636 population controls.
The heterogeneity in HLA associations with MS was demonstrated; among 100 patients, 69 extended HLA-DR-DQ genotypes were found. Three extended HLA-DR-DQ genotypes were found to be correlated to MS; HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype together with
(A) HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01,
(B) HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01, and
(C) HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01.
At the allelic level, HLA-DRB3*01:01:02 was considered protective against MS. However, when combined with HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01, this extended haplotype was considered a predisposing risk factor. This highlights the limitations as included with investigations of single alleles relative to those of extended haplotypes/genotypes.
In conclusion, with 69 genotypes presented among 100 patients, high-resolution sequencing was conducted to underscore the wide polymorphisms present among MS patients. Additional studies in larger cohorts will be of importance to define MS among the patient group not associated with HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01.
Human leucocyte antigen (HLA) alleles are very diverse and characterized by ethnicity. To date, information about the frequencies and distributions of HLA alleles among the Vietnamese population is still limited. In this study, HLA-DQB1 alleles of 2076 cord blood units from individuals belonging to Vietnam's Kinh ethnic people were genotyped using Luminex-based polymerase chain reaction sequence-specific oligonucleotide. The results of the study demonstrated that there were 23 alleles on the locus HLA-DQB1. Among those, there were six alleles with high frequencies of over 5%, including DQB1*03:01 (35.9%), DQB1*05:01 (12.8%), DQB1*03:03 (12.2%); DQB1*06:01 (7.20%), DQB1*05:02 (6.62%) and DQB1*02:01 (5.30%) and five rare alleles with low frequencies of below 0.1%. More importantly, this study for the first time reported the presence of two new rare alleles including DQB1*01:01 and DQB1*01:02. Conclusively, this study provided significant information about HLA-DQB1 alleles for further investigations and clinical applications.
Our aim was to determine whether protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) is associated with susceptibility to juvenile idiopathic arthritis (JIA). MEDLINE and EMBASE databases were searched to identify articles in which PTPN22 C1858T polymorphism was reported to be identified in JIA patients and controls. A meta-analysis was conducted to evaluate the association between PTPN22 C1858T polymorphism and RA using allelic contrast. Trial sequential analysis (TSA) was performed. Sixteen separate comparisons involving 5696 JIA patients and 9483 controls (a total of 15,179 subjects) were considered in this meta-analysis. A meta-analysis was performed with all JIA patients as well as JIA patients in each ethnic group. Meta-analysis revealed an association between the T allele of PTPN22 C1858T polymorphism and JIA in all subjects (OR, 1.322; 95% CI, 1.233–1.418; p < .001). Analysis after stratification by ethnicity indicated that the T allele was significantly associated with JIA in the European population (OR, 1.312; 95% CI, 1.2211–1.410; p < .001). However, analysis performed in the non-European population showed no significant association between the T allele and JIA. TSA indicated that the observed association between the PTPN22 polymorphism and JIA in all subjects and the European population is consistent with the existing evidence. This meta-analysis confirms that PTPN22 C1858T polymorphism is associated with susceptibility to JIA in Europeans, and that no additional studies are needed to verify these results. However, current evidence in the non-European population is insufficient, and further studies are warranted.
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