International Journal of Immunogenetics最新文献

Background: Variations in individuals’ susceptibility to coronavirus disease 2019 may be linked to the presence of genetic polymorphisms. The interferon-induced transmembrane 3 (IFITM3) has a powerful protective function by blocking viral entry into the host cell. Similarly, Interferon Lambda 3 (IFNL3) binds to its receptors and induces a variety of interferon-stimulated genes (ISGs) that inhibit viral replication. Our study aimed to investigate the potential association of IFITM3 gene polymorphism (rs12252) as well as serum IFNL3 level with COVID-19 infection, severity, and mortality.

Method: This case-control study was held during the period from July 2021 to October 2022 in Mansoura University hospitals in Egypt. We included 100 healthy controls and 154 COVID-19 patients. TaqMan real-time polymerase chain reaction was used for allelic discrimination in the genotyping of rs12252 of the IFITM3 gene. Serum IFNL-3 was assayed using the ELISA technique.

Results: The genotype and allele frequency distributions of the rs12252 showed that the frequency of the G allele and AG/GG genotypes was significantly higher in patients than in controls, with no significant association with either disease severity or outcome. Serum IFNL3 level is significantly higher among patients, with no statistically significant difference between mild and severe cases and no significant association with the outcome of COVID-19.

Conclusion: We found that the AG genotype and G allele of IFITM3 rs12252 are associated with COVID-19 infection in the Egyptian population but not with severity or outcome. Additionally, serum IFNL3 level is significantly associated with COVID-19 susceptibility but not with severity. It is associated with tachypnea and end-organ failure in severe cases. So, they are independent predictors only for developing COVID-19 infection, but not for developing severe infection.

Chronic hepatitis B (CHB) is a major risk factor for liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Genes involved in the JAK/STAT signalling pathway play a critical role in the pathogenesis of HBV-related liver diseases, especially HCC. Although SOCS1 and SOCS3 have been extensively studied, the role of SOCS6 in HBV infection and disease progression remains unclear. This study aimed to investigate the association between SOCS6 gene polymorphisms and promoter methylation with HBV-related liver diseases.

This study examined SOCS6 gene polymorphisms in a cohort of 335 patients with HBV-related liver diseases (120 with CHB, 100 with LC and 115 with HCC) and 120 healthy controls (HCs). In addition, SOCS6 promoter methylation was analysed in tumour and adjacent tissues from 41 HCC patients.

We found that the rs2062345GA genotype and the dominant genetic model were associated with an increased risk of HBV infection and HCC. The rs7228049GA genotype increased the risk of LC and HCC. Conversely, the rs7228049AA genotype and the recessive model were associated with a reduced risk of CHB, LC and HCC. The SNPs rs2062345, rs7228049 and rs11151580 were related to several clinical parameters such as AST, albumin and prothrombin levels, platelet counts in LC and HCC patients. Promoter hypermethylation of SOCS6 was more prevalent in tumour tissues, especially in larger tumours with poorer histological differentiation (p < 0.01 and p < 0.05, respectively).

SOCS6 gene variants and promoter methylation are associated with susceptibility and progression of HBV-related liver diseases. These findings suggest their potential utility as useful prognostic biomarkers for HCC.

COVID-19, caused by the SARS-CoV-2 virus, manifests with varying degrees of severity, affecting individuals worldwide. The spectrum of symptoms ranges from mild to severe, with respiratory failure being a leading cause of death. Immunological factors, particularly excessive cytokine production such as IL-18 and IL-1β, significantly contribute to disease severity. In this context, the NLRP3 inflammasome, a key component of the innate immune system, has influenced COVID-19 outcomes. This study investigated the association between single-nucleotide variants (SNVs) in the NLRP3 inflammasome and COVID-19 severity. A case–control study was conducted involving 800 adult participants infected with SARS-CoV-2, stratified into mild/moderate and severe/critical cases. Genetic associations were assessed through qPCR-based genotyping. While no association was found between SNVs in IL1B and CASP1 with COVID-19 severity, the multivariate analysis revealed that the gain-of-function SNV in the NLRP3 gene (rs35829419) was associated with a protective effect against COVID-19–related mortality. These findings suggest that genetic variations in the NLRP3 inflammasome may modulate the host response to SARS-CoV-2, highlighting potential biomarkers for disease prognosis.

Background: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease resulting from the complex interplay between genetic, environmental, and immunological factors. Genetic polymorphisms in cytokine and transcription factor genes have been proposed as key contributors to disease susceptibility and clinical heterogeneity.

Objective: To evaluate the association between selected single nucleotide polymorphisms (SNPs) in TNF-α, IL-1, IL-8, and IRF5 genes and the risk of SLE, as well as their correlation with specific organ system involvement.

Methods:We conducted a case-control study including 156 SLE patients and 104 healthy controls from the Algerian population. Seven SNPs were genotyped using TaqMan assays: IL-1 (-31 C/T and -511 C/T), TNF-α (-308 G/A and -238 G/A), IL-8 (-251 A/T), and IRF5 (-13176 A/C and -3835 G/T). Genotype and allele frequencies were compared between groups and correlated with clinical phenotypes.

Results:The immunogenetic study revealed a significant association between G allele of the -3835 G/T polymorphism of the IRF5 gene and the risk of genetic susceptibility to the lupus (p = 0.012). Stratification according to clinical manifestations has showed that the G allele of the -31 C/T polymorphism of the IL-1 gene is associated with joint damage (p = 0.024) and the A allele of -511 C/T polymorphism predisposes to hematological damage (p = 0.041) in lupus patients. Also, the A allele of the TNFα -238 G/A polymorphism was associated with neuropsychiatric impairment (p = 0.036) and the A allele of -251A/T SNP of the IL-8 gene to the joint damage (p = 0.04).

Conclusion:Our findings support a role for IRF5 and cytokine gene polymorphisms in the genetic predisposition to SLE and its clinical manifestations. These polymorphisms may serve as potential biomarkers for disease risk stratification and personalized patient management, particularly in underrepresented populations such as North Africans.