A nonsynonymous gene variant in adiponutrin gene is associated with nonalcoholic fatty liver disease severity

SOOKOIAN S; CASTANO G; BURGUEÑO A,; FERNADEZ GIANNOTTI T; MARIA SOLEDAD ROSSELLI; PIROLA CJ

JLR PAPERS IN PRESS

Federation Of American Societies For Experimental Biology

Año: 2009 vol. 20 p. 2111 - 2116

0022-2275

Objectives: We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD), and whether this SNP contributes to the severity of histological disease. Methods: Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. Results: The rs738409 G allele was significantly associated with NAFLD (p<0.001, OR 2.8 95% CI 1.5-5.2), independent of age, sex, BMI and HOMA index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed (chi2 19.9, df: 2, p<5 x10-5, adjusted for HOMA and BMI). The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed lower steatosis score (14.9%±3.9) in comparison with CG genotype (26.3%±3.5) and GG genotype (33.3%±4.0), p<0.005. The proportion of the total variation attributed to rs738409 genotypes was 5.3 % (beta 0.23±0.07, p<0.002). Conclusions: Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury possibly triggered by lipotoxicity.