Hu Yifang, Xu Kuanfeng, Jiang Lin, Zhang Lijuan, Shi He, Cui Dai
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
Genet Test Mol Biomarkers. 2018 Apr;22(4):224-236. doi: 10.1089/gtmb.2017.0243. Epub 2018 Feb 20.
In this article, we conducted an updated meta-analysis with trial sequential analysis (TSA) to refine the associations between three common single nucleotide polymorphisms (SNPs) in the CTLA-4 gene (+49A/G, CT60, and -318C/T) and Hashimoto's thyroiditis (HT).
Statistical association analyses were performed using four genetic models, including the allelic, codominant, dominant, and recessive models with the Revman 5.3, Stata 14.0, and TSA 0.9 software. For quality evaluation, the Newcastle-Ottawa Scale was used.
Our meta-analysis included 29 independent studies with low risk of bias that involved 3614 cases and 8839 controls. The pooled results indicated a significant association between the +49A/G polymorphism and an increased risk of HT in all four genetic models. Furthermore, the TSA demonstrated that the evidence of this association was robust and credible. Subgroup analysis revealed a significantly higher risk of HT in Asians compared with Caucasians associated with the +49A/G polymorphism. Surprisingly, in contrast to the results with adults, we did not find any significant association when analyzing the pediatric subgroup. For the CT60 polymorphism, a significant association with risk of HT was detected overall, and subgroup analysis revealed that this association was significant in the Asian subgroup, but not in the Caucasian subgroup. No statistically significant associations were detected in any of the investigated genetic models for the -318C/T polymorphism. However, the results of the TSA suggested that the sample sizes used for the CTLA-4 CT60 and -318C/T SNPs were insufficient.
Our meta-analysis showed significant associations between the risk of HT and both the +49A/G and CT60 polymorphisms, but not the -318C/T polymorphism. In addition, the TSA results indicated that CTLA-4 +49A/G should be considered as a biomarker for HT, whereas both the CT60 and -318C/T SNPs warrant confirmation by further studies.
在本文中，我们进行了一项更新的荟萃分析并采用序贯试验分析（TSA），以明确细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因中的三种常见单核苷酸多态性（SNP）（+49A/G、CT60和-318C/T）与桥本甲状腺炎（HT）之间的关联。
使用四种遗传模型进行统计关联分析，包括等位基因模型、共显性模型、显性模型和隐性模型，采用Revman 5.3、Stata 14.0和TSA 0.9软件。对于质量评估，使用纽卡斯尔-渥太华量表。
我们的荟萃分析纳入了29项偏倚风险较低的独立研究，涉及3614例病例和8839例对照。汇总结果表明，在所有四种遗传模型中，+49A/G多态性与HT风险增加之间存在显著关联。此外，TSA表明这种关联的证据是可靠且可信的。亚组分析显示，与+49A/G多态性相关的亚洲人患HT的风险显著高于白种人。令人惊讶的是，与成人结果相反，在分析儿科亚组时，我们未发现任何显著关联。对于CT60多态性，总体上检测到与HT风险存在显著关联，亚组分析显示这种关联在亚洲亚组中显著，但在白种人亚组中不显著。在任何研究的遗传模型中，均未检测到-318C/T多态性存在统计学显著关联。然而，TSA结果表明，用于CTLA-4 CT60和-318C/T SNPs的样本量不足。
我们的荟萃分析表明，HT风险与+49A/G和CT60多态性均存在显著关联，但与-318C/T多态性无关。此外，TSA结果表明，CTLA-4 +49A/G应被视为HT的生物标志物，而CT60和-318C/T SNPs均需进一步研究予以证实。
