Pellenz Felipe Mateus, Dieter Cristine, Lemos Natália Emerim, Bauer Andrea Carla, Souza Bianca Marmontel de, Crispim Daisy
Hospital de Clínicas de Porto Alegre, Serviço de Endocrinologia, Porto Alegre, RS, Brazil.
Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre, RS, Brazil.
Genet Mol Biol. 2021 May 3;44(2):e20200425. doi: 10.1590/1678-4685-GMB-2020-0425. eCollection 2021.
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.
自身免疫性疾病的特征是自身耐受性丧失，导致免疫介导的组织破坏和慢性炎症。酪氨酸激酶2（TYK2）蛋白在免疫和凋亡途径中起关键作用。研究报道了TYK2基因单核苷酸多态性（SNP）与自身免疫性疾病之间的关联；然而，结果仍无定论。因此，我们进行了一项系统评价并随后进行荟萃分析。进行文献检索以查找研究TYK2 SNP与自身免疫性疾病（多发性硬化症、系统性红斑狼疮、克罗恩病、溃疡性结肠炎、银屑病、类风湿性关节炎、1型糖尿病和炎症性肠病）之间关联的研究。使用Stata 11.0软件中的随机（REM）或固定（FEM）效应模型计算合并比值比（OR）及95%置信区间（CI）。34篇文章符合纳入荟萃分析的条件，包含9种不同的SNP：rs280496、rs280500、rs280523、rs280519、rs2304256、rs12720270、rs12720356、rs34536443和rs35018800。荟萃分析结果显示，rs2304256、rs12720270、rs12720356、rs34536443和rs35018800 SNP的次要等位基因与预防自身免疫性疾病有关。此外，rs280519 SNP的A等位基因与系统性红斑狼疮的风险有关。我们的荟萃分析表明，TYK2基因中的rs2304256、rs12720270、rs12720356、rs34536443、rs35018800和rs280519 SNP与不同的自身免疫性疾病有关。
