International Journal of Immunogenetics最新文献

This study investigates the distribution of human leukocyte antigen (HLA)-DRB4 alleles in HLA-DRB1*07:01-positive haplotypes within a Saudi cohort of 313 individuals. It identifies strong linkage disequilibrium between HLA-DRB1*07:01 and specific alleles. The most prevalent HLA-DRB1∼DQB1 combination identified is DRB1*07:01∼DQB1*02:02. Additionally, for the HLA-DRB1*07:01∼DQB1*03:03 association, DRB4*01:01 was found to be more common than the DRB4*01:03N allele. The most frequently observed extended haplotype is HLA-A*02:01∼C*06:02∼B*50:01∼DRB1*07:01∼DRB4*01:03∼DQA1*02:01∼DQB1*02:02∼DPA1*01:03∼DPB1*04:01. These findings emphasize the distinct genetic characteristics of the Saudi population and contribute to understanding haplotypic diversity, particularly the prevalence of HLA-DR7-related alleles and their implications for disease susceptibility and transplantation compatibility.

We performed a meta-analysis to study the relationship between HLA-G 14-bp insertion/deletion polymorphism and recurrent spontaneous abortion (RSA). All literature was searched from PubMed, Web of Science, Embase and Wanfang databases. Statistical analyses were performed by the STATA software (Version 16.0). A total of 35 studies were analysed which included 3652 women with RSA and 3331 normal control subjects. The current meta-analysis revealed that 14-bp insertion/deletion polymorphism has a significant association with RSA (I vs. D: OR: 1.17; 95% CI (1.05–1.30); II + ID vs. DD: OR: 1.33; 95% CI (1.11–1.59); II vs. DD: OR: 1.34; 95% CI (1.07–1.66); ID vs. DD: OR: 1.30; 95% CI (1.08–1.58)). Subgroup analysis by the number of abortions indicated that there was no significant association between HLA-G 14-bp insertion/deletion polymorphism and RSA risk in women with two or more abortions. However, HLA-G 14-bp insertion/deletion polymorphism was associated with the risk of RSA in women with three or more abortions as well as the overall population (I vs. D: OR: 1.26; 95% CI (1.04–1.52); II + ID vs. DD: OR: 1.47; 95% CI (1.09–1.98); II vs. DD: OR: 1.52; 95% CI (1.08–2.13); ID vs. DD: OR: 1.45; 95% CI (1.06–1.99)). Subgroup analysis by ethnicity indicated that HLA-G 14-bp insertion/deletion polymorphism increased RSA risk in both Asian ancestry group (II + ID vs. DD: OR: 1.35; 95% CI (1.06–1.73); ID vs. DD: OR: 1.37; 95% CI (1.06–1.78)) and European ancestry group (I vs. D: OR: 1.25; 95% CI (1.08–1.45); II vs. ID + DD: OR: 1.48; 95% CI (1.14–1.91); II vs. DD: OR: 1.61; 95% CI (1.19–2.18)). A p_OR value of < 0.05 was considered statistically significant for these analyses. Our current meta-analysis demonstrated that the HLA-G 14-bp insertion/deletion polymorphism increased the risk of RSA in Asian ancestry group and European ancestry group.

C1q deficiency is a rare autosomal recessive disease associated with recurrent skin lesions, chronic infections and an increased risk of autoimmune disorders, particularly systemic lupus erythematosus (SLE) or SLE-like disorders. Additionally, it has been linked to chronic glomerulonephritis and renal failure. C1q is the initial subcomponent of the classical pathway of the complement system and serves as a crucial linking factor between innate and acquired immunity. The C1 complex comprises three proteins: C1q, C1r and C1s. C1q comprises three chains: the A, B and C. The C1QB gene encodes the B-chain polypeptide of the serum complement subcomponent C1q. We report the case of an Iranian girl from a consanguineous family who suffers from C1q deficiency, presenting with some SLE symptoms that have not previously been described in the literature. She presented with progressive weakness in walking, tissue injury, skin lesions and subjective cognitive complaints regarding concentration and memory. The proband exhibited mild asymmetric uptake in the pelvic region, resulting in a waddling gait. Additionally, she showed abnormal circulating homocysteine levels, skin abnormalities and early inflammatory arthritis symptoms associated with SLE. Whole-exome sequencing (WES) was performed on the proband. A novel homozygous likely pathogenic missense variant in the C1QB gene, NM_001378156.1:c.263G>A, was identified. The variant was confirmed by Sanger sequencing in the proband, her parents and her healthy sister. This case highlights the significance of identifying a novel mutation in the C1QB gene, which expands the clinical spectrum of C1q deficiency. This finding contributes to the broader understanding of the disease's phenotype, helping to refine diagnostic criteria, particularly in cases with atypical manifestations. Furthermore, identifying such mutations in consanguineous families aids in genetic counselling and early diagnosis, allowing for better clinical management and prevention strategies.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global health, with Morocco reporting over 1.2 million confirmed cases and more than 16,300 deaths. The severity of COVID-19 varies, ranging from asymptomatic cases to mild symptoms, acute respiratory failure and death. Genetic factors are believed to influence individual responses to the virus. This study investigates the association between two common single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs)—TLR2 rs3804099 (+597 C/T) and TLR4 rs4986790 (+896 A/G)—and disease severity and inflammatory markers in Moroccan COVID-19 patients. A total of 452 COVID-19 patients (259 with mild/moderate disease and 193 with severe disease) were included. TLR2 and TLR4 SNPs were genotyped using a predesigned TaqMan real-time allelic discrimination assay. Complete blood count samples, along with levels of C-reactive protein (CRP), ferritin, procalcitonin and D-dimer, were assessed using automated methods. No significant associations were observed between either SNP in TLR2 and TLR4 and disease severity under various genetic models. However, in severe cases, TLR4 rs4986790 showed a significant association with ferritin levels (p = 0.0002) and lymphocyte count (p < 0.0001). TLR2 rs3804099 was linked to CRP levels in severe patients (p = 0.036). No associations were observed with anti-receptor-binding domain (RBD) IgG or anti-N IgG levels in severe cases (p > 0.05). These findings suggest that although TLR4 and TLR2 polymorphisms are not directly associated with COVID-19 severity, they may influence the inflammatory response. Specifically, TLR4 rs4986790 and TLR2 rs3804099 appear to modulate ferritin and CRP levels, potentially impacting disease progression in severe cases.

Several studies suggest that a deficiency in vitamin D might be a potential risk factor for developing diabetic retinopathy. Research has extensively studied vitamin D receptor genes, such as the FokI gene polymorphisms, and found links between these genetic variations and susceptibility to diabetic retinopathy across different populations. This study aimed to investigate how vitamin D deficiency and vitamin D receptor FokI gene polymorphisms influence the risk of diabetic retinopathy complications in individuals with Type 2 diabetes mellitus. This was a hospital-based case-control research with 153 diabetic retinopathy patients, 153 Type 2 diabetes mellitus patients, and 153 age- and sex-matched healthy controls. Through the collection and analysis of clinical and demographic data, the study assessed the diabetic retinopathy risk factors. The FokI genotypes were determined by analysing DNA isolated from blood samples using polymerase chain reaction and agarose gel electrophoresis. Diabetic retinopathy patients had a much higher prevalence of VDD (OR = 6.24, 95% CI = 3.14–12.39; p < 0.001) than Type 2 diabetes patients and healthy controls. Furthermore, diabetic retinopathy patients had significantly higher frequencies of the FokI ff genotype (OR = 2.04; 95% CI = 1.24–3.75; p = 0.005) and the f allele (OR = 1.56; 95% CI = 1.18–2.06; p = 0.001) than Type 2 diabetes patients and healthy controls. These results indicate that vitamin D deficiency and vitamin D receptor FokI gene polymorphisms are risk factors for the onset and progression of diabetic retinopathy. There is a significant correlation between vitamin D deficiency and the development of diabetic retinopathy. Moreover, the FokI gene of the ff genotype and the f allele have been linked to an increased risk of developing diabetic retinopathy complications in patients with a history of Type 2 diabetes mellitus in the Ethiopian population under study.

Some associations between Treponema pallidum (TP) susceptibility and human leukocyte antigen (HLA) loci at low resolution have been reported. However, the data for TP infection and HLA alleles at high resolution are limited. The purpose of this study was to perform a high-resolution screen for HLA alleles that confer susceptibility to TP infection in the Chinese Han population. A total of 184 individuals with TP infection were included in the study, and 254 unrelated healthy blood donors were included in the control group. The samples were genotyped for the HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 loci using next-generation sequencing (NGS) technology. The correlations between TP infection and the alleles and haplotypes of HLA loci were determined by statistical analysis. Five HLA alleles, including HLA-A*32:01 (0.00% vs. 1.57%, p = 0.024), -B*52:01 (1.36% vs. 4.13%, p = 0.025), -C*01:02 (22.55% vs. 16.54%, p = 0.029), -C*04:03 (1.63% vs. 0.2%, p = 0.046) and -DQB1*05:03 (1.63% vs. 4.13%, p = 0.046), are potentially associated with TP infection. However, no significant difference was detected after p value correction. The frequency of the HLA-A*33:03-C*03:02-B*58:01-DRB1*03:01-DQB1*02:01-DPB1*05:01 haplotype in the control group was greater than that in the TP infection group (p = 0.002). In contrast, the frequency of the HLA-A*02:07-C*01:02-B*46:01-DRB1*08:03-DQB1*06:01-DPB1*02:01, HLA-A*11:01-C*03:04-B*13:01-DRB1*09:01-DQB1*03:03-DPB1*05:01, HLA-A*11:01-C*07:02-B*40:01-DRB1*08:03-DQB1*06:01-DPB1*02:01 and HLA-A*30:01-C*06:02-B*13:02-DRB1*07:01-DQB1*02:02-DPB1*02:01 haplotypes were lower in the control group than in the TP infection group (p < 0.05). HLA-C*01:02 and -C*04:03 may confer susceptibility to TP infection, whereas A*32:01, -B*52:01 and -DQB1*05:03 may protect against TP infection. These data are helpful in preventing and controlling TP transmission.

Previous studies of genetic contributions to risk of childhood asthma have implicated common variants with small effect sizes. Some studies using exome sequence data have reported associations with rare coding variants having larger effects on risk, notably an analysis of 145,000 subjects which found association with loss of function (LOF) variants in FLG, the gene coding for filaggrin. Here, we report the results of an analysis of rare nonsynonymous and LOF variants, carried out on the full UK Biobank cohort of 470,000 exome-sequenced participants. The phenotype of childhood asthma was defined as reporting asthma with onset before 18. Regression analysis was applied to gene-wise tests for association of LOF and nonsynonymous variants. Forty-five tests using different pathogenicity predictors were applied to the first cohort of 200,000 participants. Subsequently, the 100 genes showing strongest evidence for association were analysed in the second cohort of 270,000 participants, using only the best-performing predictor for each gene. For FLG, separate analyses were carried out for participants with atopic dermatitis. Three genes achieved statistical significance after correction for testing these 100 genes: FLG, IL33 and PRKCQ. The effects on asthma risk and frequencies of variants in different functional categories were characterised for these genes. Damaging coding variants were associated with increased risk of asthma in FLG and IL33 but reduced risk in PRKCQ. FLG LOF variants were also associated with the risk of atopic dermatitis, and their effect on asthma risk was higher in people who reported a diagnosis of atopic dermatitis. Rare coding variants in a small number of genes have important effects on asthma risk. Further study of individual variant effects might elucidate mechanisms of pathogenesis. This research has been conducted using the UK Biobank Resource.