Abstract
A nonsynonymous E167K (rs58542926 C/T) variant in TM6SF2 gene was recently associated with nonalcoholic fatty liver disease (NAFLD). We explored the association between E167K and plasma concentrations of alanine (ALT) and aspartate (AST) aminotransferases through a meta-analysis. We also estimated the strength of the effect across diverse liver phenotypes, including NAFLD and chronic viral hepatitis; fourteen studies were included. We found that ALT (p = 3.2 × 10−6, n = 94,414) and AST (p = 0007, n = 93,809) levels were significantly associated with rs58542926 in NAFLD. By contrast, rs58542926 was not associated with either ALT (p = 0.24, n = 4187) or AST (p = 0.17, n = 2678) levels in four studies on chronic hepatitis. In conclusion, the results of the pooled estimates in patients with NAFLD showed that carriers of the T allele (EK + KK), when compared with homozygous subjects for the C allele (EE genotype) have increased levels of aminotransferases; however, this increase represents –2.5 (9.8%) and 1.2 (5%) IU/L of ALT and AST respectively, which is fairly small compared with the large effect of PNPLA3- rs738409-G allele that is associated with a –28% increase in serum ALT.
Highlights
The large body of evidence derived from epidemiological studies on the prevalence of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD) has uncovered an unexpected but biologically plausible association between aminotransferases and all of the individual components of the metabolic syndrome (MetS), as recently reviewed[2]
The results of the first genome-wide association study (GWAS) on nonalcoholic fatty liver disease (NAFLD) found an association between the rs738409 and serum ALT levels, this association was only restricted to the Hispanic group, which was the ethnic group with the greatest prevalence of hepatic steatosis in the recruited population[10]
Summarized evidence from the following-up candidate-gene association studies demonstrated that carriage of the homozygous state for the rs738409-G allele is associated with a ~28% increase in serum ALT levels[11]
Summary
The large body of evidence derived from epidemiological studies on the prevalence of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD) has uncovered an unexpected but biologically plausible association between aminotransferases and all of the individual components of the metabolic syndrome (MetS), as recently reviewed[2]. We estimated the strength of the effect of rs58542926 on both circulating ALT and AST across different populations and diverse liver phenotypes, including NAFLD and chronic viral hepatitis.
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