The roles of transmembrane 6 superfamily member 2 rs58542926 polymorphism in chronic liver disease: A meta-analysis of 24,147 subjects.

Background 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. Methods Systematic literature research of PubMed, Web of Science, Embase, and CNKI was performed to identify eligible studies for pooled analyses. I-2 statistics were employed to assess between-study heterogeneities. If I-2 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. Results 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-2 = 47%; recessive model: p < 0.0001, OR = 2.94, 95% CI = 2.05-4.20, I-2 = 0%; over-dominant model: p < 0.0001, OR = 1.34, 95% CI = 1.23-1.47, I-2 = 0%; allele model: p < 0.0001, OR = 0.68, 95% CI = 0.63-0.73, I-2 = 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). Conclusions 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.