Cytokine and IRF5 Gene Polymorphisms Associated With Susceptibility and Organ Damage in Systemic Lupus Erythematosus.

IF 1.1 4区 医学 Q3 GENETICS & HEREDITY
Ines Allam, Yousra Hassinet, Chahrazad Zeghichi, Lylia Meriem Berkani, Brahim Belaid, Sihem Oulakrouz, Messaoud Saidani, Soraya Ayoub, Reda Djidjik
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引用次数: 0

Abstract

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.

细胞因子和IRF5基因多态性与系统性红斑狼疮易感性和器官损伤相关。
背景:系统性红斑狼疮(SLE)是一种多因素自身免疫性疾病,是遗传、环境和免疫因素复杂相互作用的结果。细胞因子和转录因子基因的遗传多态性被认为是疾病易感性和临床异质性的关键因素。目的:评估TNF-α、IL-1、IL-8和IRF5基因中选定的单核苷酸多态性(snp)与SLE风险的关系,以及它们与特定器官系统受累的相关性。方法:我们进行了一项病例对照研究,包括来自阿尔及利亚人群的156名SLE患者和104名健康对照者。采用TaqMan方法对7个snp进行基因分型:IL-1 (-31 C/T和-511 C/T)、TNF-α (-308 G/A和-238 G/A)、IL-8 (-251 A/T)和IRF5 (-13176 A/C和-3835 G/T)。基因型和等位基因频率在组间比较,并与临床表型相关。结果:免疫遗传学研究显示,IRF5基因-3835 G/T多态性的G等位基因与狼疮遗传易感性风险之间存在显著相关性(p = 0.012)。根据临床表现分层发现,狼疮患者IL-1基因-31 C/T多态性的G等位基因与关节损伤相关(p = 0.024), -511 C/T多态性的A等位基因易导致血液学损伤(p = 0.041)。此外,TNFα -238 G/A多态性的A等位基因与神经精神障碍相关(p = 0.036), IL-8基因-251A/T SNP的A等位基因与关节损伤相关(p = 0.04)。结论:我们的研究结果支持IRF5和细胞因子基因多态性在SLE遗传易感性及其临床表现中的作用。这些多态性可以作为疾病风险分层和个性化患者管理的潜在生物标志物,特别是在代表性不足的人群中,如北非人。
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来源期刊
CiteScore
4.70
自引率
0.00%
发文量
48
审稿时长
6-12 weeks
期刊介绍: The International Journal of Immunogenetics (formerly European Journal of Immunogenetics) publishes original contributions on the genetic control of components of the immune system and their interactions in both humans and experimental animals. The term ''genetic'' is taken in its broadest sense to include studies at the evolutionary, molecular, chromosomal functional and population levels in both health and disease. Examples are: -studies of blood groups and other surface antigens- cell interactions and immune response- receptors, antibodies, complement components and cytokines- polymorphism- evolution of the organisation, control and function of immune system components- anthropology and disease associations- the genetics of immune-related disease: allergy, autoimmunity, immunodeficiency and other immune pathologies- All papers are seen by at least two independent referees and only papers of the highest quality are accepted.
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