A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population.

OBJECTIVE: Mechanisms explaining the relationship between non-alcoholic fatty liver disease (NAFLD), obesity and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients. DESIGN AND METHODS: Patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped. RESULTS: 470 patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (p<0.001) and aspartate aminotransferase (p<0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (p<0.001), lobular inflammation (p<0.001), and ballooning (p=0.002), but not with liver fibrosis, anthropometry or insulin resistance. No significant difference in liver histology, anthropometric or metabolic parameters was found between carriers and non-carriers of the APOC3 variant. CONCLUSIONS: PNPLA3 polymorphism rs738409 is associated with NASH independently of metabolic factors. We found no association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD. Copyright © 2013 The Obesity Society.