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.
Highlights
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
For the purpose of testing the hypothesis of a relation between the rs738409 and the histological severity of NAFLD, we included in the analysis only those patients that had histopathologic evidence of fatty liver disease, either simple steatosis or nonalcoholic steatohepatitis (NASH), on liver biopsy performed within this study (n = 103)
40 patients were assigned to the simple steatosis group and 63 were included in the NASH group
Summary
The study involved a total of 266 unrelated individuals (80 males and 186 females), of which 172 patients had features of NAFLD and 94 were control subjects. For the purpose of testing the hypothesis of a relation between the rs738409 and the histological severity of NAFLD, we included in the analysis only those patients that had histopathologic evidence of fatty liver disease, either simple steatosis or NASH, on liver biopsy performed within this study (n = 103) (details in the liver biopsy description). In addition to the standard heath examination, all the control individuals were subjected to liver US. They were included in the study if they did not have evidence of fatty change or biochemical abnormalities. Written consent from individuals was obtained in accordance with the procedures approved by the ethical committee of our institution
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