Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) and the closely associated metabolic syndrome is high and is related to risk factors such as obesity and type 2 diabetes. A genetic basis for NAFLD has been suggested, but only few causal genes have been identified. The most significant association reported to date is the robust association of the PNPLA3 I148M variant with susceptibility to NAFLD. We therefore hypothesized that the PNPLA2 gene might also be involved in NAFLD pathogenesis, because of its close sequence similarity with PNPLA3 and its possible involvement in ectopic fat accumulation.
Methods: In this study, we investigated the association of PNPLA2 polymorphisms with the development of non-alcoholic fatty liver disease in a prospectively recruited Belgian obese population comprising 633 individuals with varying degrees of fatty liver disease. We selected 3 PNPLA2 SNPs for genotyping, including 2 tagSNPs that cover most information on common genetic variation in the selected region.
Results: After performing linear regression analysis, we found that 2 of the analyzed PNPLA2 SNPs were associated with anthropometric and metabolic parameters. In our subcohort of patients that underwent liver biopsy (n=372/633 or 58.7%), we assessed the influence of the PNPLA2 variants on the severity of histologically determined liver damage, but we did not find convincing evidence for association.
Conclusion: Although we found evidence for moderate association between PNPLA2 tagSNPs and anthropometric and metabolic parameters in our cohort, no evidence for association between polymorphisms in the PNPLA2 gene and the presence and severity of NAFLD was identified.
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