Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Mol Genet Genomic Med. 2019 Aug;7(8):e824. doi: 10.1002/mgg3.824. Epub 2019 Jul 15.
Some genetic association studies tried to investigate potential associations of transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms with chronic liver disease. However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between TM6SF2 polymorphisms and chronic liver disease in a larger pooled population.
Systematic literature research of PubMed, Web of Science, Embase, and CNKI was performed to identify eligible studies for pooled analyses. I statistics were employed to assess between-study heterogeneities. If I was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses.
Totally 28 studies were included for analyses (13,137 cases and 11,010 controls). The pooled analyses showed that rs58542926 polymorphism was significantly associated with chronic liver disease in overall population (dominant model: p < 0.0001, OR = 0.70, 95% CI = 0.64-0.76, I = 47%; recessive model: p < 0.0001, OR = 2.94, 95% CI = 2.05-4.20, I = 0%; over-dominant model: p < 0.0001, OR = 1.34, 95% CI = 1.23-1.47, I = 0%; allele model: p < 0.0001, OR = 0.68, 95% CI = 0.63-0.73, I = 47%), and these significant findings were further confirmed in both Asians and Caucasians. Stratified analyses by type of disease revealed similar positive results in hepatocellular carcinoma (HCC), cirrhosis, alcoholic liver disease (ALD) and NAFLD (Nonalcoholic fatty liver disease), but not in chronic hepatitis B infection (CHB) and chronic hepatitis C infection (CHC).
These results suggested that TM6SF2 rs58542926 could be used to identify individuals at higher susceptibility to chronic liver disease, especially for HCC, cirrhosis, ALD, and NAFLD.
一些遗传关联研究试图探讨跨膜 6 超家族成员 2（TM6SF2）多态性与慢性肝病之间的潜在关联。然而，这些研究的结果并不一致。因此，我们进行了本次荟萃分析，以在更大的汇总人群中探讨 TM6SF2 多态性与慢性肝病之间的关系。
系统检索 PubMed、Web of Science、Embase 和中国知网（CNKI）中的文献，以确定纳入荟萃分析的研究。采用 I ² 统计量评估研究间的异质性。如果 I ² 大于 50%，则采用随机效应模型（REMs）进行数据合并。否则，采用固定效应模型（FEMs）进行综合分析。
共纳入 28 项研究进行分析（病例 13137 例，对照 11010 例）。汇总分析结果显示，rs58542926 多态性与总体人群的慢性肝病显著相关（显性模型：p<0.0001，OR=0.70，95%CI=0.64-0.76，I ² =47%；隐性模型：p<0.0001，OR=2.94，95%CI=2.05-4.20，I ² =0%；超显性模型：p<0.0001，OR=1.34，95%CI=1.23-1.47，I ² =0%；等位基因模型：p<0.0001，OR=0.68，95%CI=0.63-0.73，I ² =47%），且这些显著关联在亚洲人和高加索人群中均得到进一步证实。按疾病类型进行分层分析显示，在肝细胞癌（HCC）、肝硬化、酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）中也得到了类似的阳性结果，但在慢性乙型肝炎感染（CHB）和慢性丙型肝炎感染（CHC）中未得到阳性结果。
这些结果表明，TM6SF2 rs58542926 可用于识别慢性肝病易感个体，特别是 HCC、肝硬化、ALD 和 NAFLD。
