title: A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity.
abstract: 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. 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. 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, body mass index (BMI), and Homeostasis Model Assessment (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, degree of freedom (df): 2, P < 5 x 10(-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 a lower steatosis score (14.9% +/- 3.9) in comparison with the 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). 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.
authors.affiliation: Laboratory of Clinical and Molecular Hepatology, Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research, University of Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina. ssookoian@lanari.fmed.uba.ar
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.forename: Gustavo O
authors.initials: GO
authors.lastname: Castaño
authors.forename: Adriana L
authors.initials: AL
authors.lastname: Burgueño
authors.forename: Tomas Fernández
authors.initials: TF
authors.lastname: Gianotti
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Rosselli
authors.forename: Carlos Jose
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C436316:adiponutrin