TM6 SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism.

Background & Aims A common non-synonymous polymorphism, E167K, in transmembrane six superfamily member 2 ( TM6 SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6 SF2 variants and liver lesions in chronic hepatitis C. Patients and Methods 148 consecutive patients with biopsy proven anti- HCV/ HCV- RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6 SF2 E167K and PNPLA3 I148M variants. Results The score of liver steatosis was higher in the 18 patients with TM6 SF2 E167K variant (mean 1.9 ± 1.3) than in the 130 homozygotes for TM6 SF2 167E allele (1.1 ± 1.1, P = 0.02), and the prevalence of a steatosis score ≥ 3 was 33.3% vs. 12.3% respectively ( P = 0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6 SF2 E167K and PNPLA3 M148M variants and waist circumference ( P = 0.0376, P = 0.0069 and P = 0.0273 respectively). Conclusions This is the first demonstration that TM6 SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C. [ABSTRACT FROM AUTHOR]