International Journal of Immunogenetics最新文献

The main objective of the study was to determine the association of genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488) polymorphisms with rheumatoid arthritis (RA) from the population of Pakistan. Blood samples of 300 RA patients and 300 healthy controls were taken from different hospitals in Pakistan. Extraction of DNA was carried out; a specific region of DNA was amplified using PCR. Polymorphic analysis was performed for genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488). The demographic parameters, like age, showed statistically significant association and increased the risk of the disease up to 2-fold (odds ratio [OR] = 2.57; 95% confidence interval [CI] = 1.60–4.12; p = 0.0001). Gender and family history did not show any significant association with arthritis (OR = 1.12; 95% CI = 0.69–1.81; p = 0.6260; OR = 0.70; 95% CI = 0.44–1.11; p = 0.1313, respectively). In the case of smoking status, the difference was statistically significant for both smokers and non-smokers. In smokers, there was a decreased risk of RA (OR = 0.45; 95% CI = 0.28–0.73; p = 0.0011), and in non-smokers, there was an increased risk of disease up to 2-fold (OR = 2.17; 95% CI = 1.36–3.47; p = 0.0011). In AIRE gene, heterozygous (AG) of rs2075876 showed a highly significant association with increased risk of RA up to 3-fold (OR = 3.39; 95% CI = 2.08–5.54; p = 0.0001), whereas homozygous mutant (GG) also showed significant association (OR = 0.43; 95% CI = 0.26–0.72; p = 0.0014) but with decreased risk. In CD40 gene, heterozygous (AG) of rs4810485 showed significant association with a decreased risk of RA (OR = 0.59; 95% CI = 0.377–0.945; p = 0.027), whereas the homozygous mutant (GG) of rs4810485 showed highly significant association by increasing risk of up to 4-fold (OR = 4.318; 95% CI = 2.553–7.303; p = 0.0001). In HLA-DRB1 gene, heterozygous (CT) of rs6457617 showed significant association with a decreased risk of disease (OR = 0.52; 95% CI = 0.35–0.85; p = 0.007), whereas the homozygous mutant (TT) of rs6457617 showed highly significant association by increasing the risk of RA up to 4-fold (OR = 4.37; 95% CI = 2.55–7.47; p = 0.0001). In the TRAF1/C5 gene, heterozygosity (AG) of rs10818488 showed a significant association with an increased risk of disease up to 4-fold (OR = 4.06; 95% CI = 2.38–6.98; p = 0.0001). Highly significant associations of genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488) polymorphisms were observed with RA.

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.