IL-6、IL-10基因多态性与自身免疫性甲状腺疾病易感性的Meta分析

IL-6 and IL-10 gene polymorphisms and susceptibility to autoimmune thyroid disease:a Meta analysis

目的阐明白细胞介素(IL)-6、IL-10基因多态性与自身免疫性甲状腺疾病(AITD)之间的关系。方法通过PubMed、Web of Science、中国知网(CNKI)、Embase、万方数据库和维普网等数据库进行文献检索,将国内外的IL-6、IL-10基因多态性与AITD有关的文献纳入研究,时限为数据库建库至2021年7月。采用STATA 16.0软件进行Meta分析,以比值比(OR)和95%置信区间(CI)作为效应指标,根据异质性结果选用随机效应或固定效应模型,通过亚组分析探讨其异质性来源;使用漏斗图、Egger′s检验评价发表偏倚。结果最终纳入19篇文献,均为英文;包括IL-6基因12篇、IL-10基因11篇,其中同时包含IL-6和IL-10基因4篇。在全人群中,与AITD发病有关联的位点为IL-6基因-174 G/C位点(GG比CC+GC:OR=1.94,95%CI为1.01~3.76),IL-6基因-572 G/C位点(GG+GC比CC:OR=0.49,95%CI为0.29~0.84;GG比CC+GC:OR=0.76,95%CI为0.60~0.96;GG+CC比GC:OR=0.63,95%CI为0.49~0.81),IL-10基因-819 T/C位点(TT+TC比CC:OR=1.84,95%CI为1.01~3.34;T比C:OR=1.59,95%CI为1.00~2.51),IL-10基因-1082 A/G位点(AA+AG比GG:OR=0.77,95%CI为0.64~0.92;AA比GG+AG:OR=2.03,95%CI为1.16~3.58;A比G:OR=0.76,95%CI为0.61~0.94)。亚组分析结果显示,在亚洲人中,与AITD发病有关联的位点为IL-6基因-174 G/C位点(GG比CC+GC:OR=4.61,95%CI为1.11~19.23;G比C:OR=0.65,95%CI为0.44~0.97),IL-6基因-572 G/C位点(GG比CC+GC:OR=0.64,95%CI为0.41~0.99;GG+CC比GC:OR=0.60,95%CI为0.38~0.94),IL-10基因-819 T/C位点(TT+TC比CC:OR=2.51,95%CI为1.48~4.25;T比C:OR=1.91,95%CI为1.05~3.46),IL-10基因-1082 A/G位点(AA+AG比GG:OR=0.66,95%CI为0.52~0.84;AA比GG+AG:OR=2.83,95%CI为1.54~5.21;A比G:OR=0.66,95%CI为0.53~0.82)。结论IL-6-174 G/C、IL-6-572 G/C、IL-10-819 T/C和IL-10-1082 A/G多态性与AITD的易感性相关,尤其在亚洲人中更显著。

Objective To clarify the relationship between interleukin(IL)-6,IL-10 gene polymorphisms and autoimmune thyroid disease(AITD).Methods Literature search was conducted through databases such as PubMed,Web of Science,CNKI,Embase,Wanfang Database and VIP.com,and domestic and foreign literatures related to IL-6,IL-10 gene polymorphisms and AITD were included in the study.The time limit was from the self-built of the databases to July 2021.Meta-analysis was performed with STATA 16.0 software,the odds ratio(OR)and 95%confidence interval(CI)were used as effect indicators,random-effect or fixed-effect model was selected according to the heterogeneity results,and the source of heterogeneity was explored through subgroup analysis.Publication bias was assessed using funnel plots and Egger's test.Results Finally,19 literatures were included,all in English.There were 12 studies on IL-6 genes and 11 studies on IL-10 genes,including 4 studies on both IL-6 and IL-10 genes.In the whole population,the loci associated with AITD were IL-6-174 G/C site(GG vs CC+GC:OR=1.94,95%CI=1.01-3.76),IL-6-572 G/C site(GG+GC vs CC:OR=0.49,95%CI=0.29-0.84;GG vs CC+GC:OR=0.76,95%CI=0.60-0.96;GG+CC vs GC:OR=0.63,95%CI=0.49-0.81),IL-10-819 T/C site(TT+TC vs CC:OR=1.84,95%CI=1.01-3.34;T vs C:OR=1.59,95%CI=1.00-2.51),and IL-10-1082 A/G site(AA+AG vs GG:OR=0.77,95%CI=0.64-0.92;AA vs GG+AG:OR=2.03,95%CI=1.16-3.58;A vs G:OR=0.76,95%CI=0.61-0.94).The results of subgroup analysis showed that in Asian population,the loci associated with AITD were IL-6-174 G/C site(GG vs CC+GC:OR=4.61,95%CI=1.11-19.23;G vs C:OR=0.65,95%CI=0.44-0.97);IL-6-572 G/C site(GG vs CC+GC:OR=0.64,95%CI=0.41-0.99;GG+CC vs GC:OR=0.60,95%CI=0.38-0.94);IL-10-819 T/C site(TT+TC vs CC:OR=2.51,95%CI=1.48-4.25;T vs C:OR=1.91,95%CI=1.05-3.46);and IL-10-1082 A/G site(AA+AG vs GG:OR=0.66,95%CI=0.52-0.84;AA vs GG+AG:OR=2.83,95%CI=1.54-5.21;A vs G:OR=0.66,95%CI=0.53-0.82).Conclusion IL-6-174 G/C,IL-6-572 G/C,IL-10-819 T/C and IL-10-1082 A/G polymorphisms are associated with the susceptibility to AITD,especially in Asians.