Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis

Abstract Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.

摘要：自身免疫性疾病（Autoimmune Diseases）以自身耐受丧失为核心特征，可导致免疫介导的组织损伤与慢性炎症。酪氨酸激酶2（Tyrosine Kinase 2, TYK2）蛋白在免疫应答与细胞凋亡通路中发挥关键作用。已有研究报道TYK2基因的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）与自身免疫性疾病存在关联，但相关研究结论尚未达成共识。因此，本研究开展系统评价并辅以荟萃分析（meta-analysis）。我们通过文献检索，筛选了探讨TYK2基因SNPs与自身免疫性疾病——包括多发性硬化、系统性红斑狼疮、克罗恩病、溃疡性结肠炎、银屑病、类风湿关节炎、1型糖尿病及炎症性肠病——关联的相关研究。本研究采用Stata 11.0软件，通过随机效应模型（Random Effects Model, REM）或固定效应模型（Fixed Effects Model, FEM）计算合并比值比（Odds Ratio, OR）及其95%置信区间（Confidence Interval, CI）。最终有34篇文献符合荟萃分析的纳入标准，共涉及9个不同的SNPs位点：rs280496、rs280500、rs280523、rs280519、rs2304256、rs12720270、rs12720356、rs34536443及rs35018800。荟萃分析结果显示，rs2304256、rs12720270、rs12720356、rs34536443及rs35018800这5个SNPs的次要等位基因与自身免疫性疾病的发病风险降低显著相关。此外，rs280519位点的A等位基因与系统性红斑狼疮的发病风险升高相关。本研究的荟萃分析证实，TYK2基因的rs2304256、rs12720270、rs12720356、rs34536443、rs35018800及rs280519这6个SNPs位点与不同类型的自身免疫性疾病存在显著关联。