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A gene variant of PNPLA3 , but not of APOC3 , is associated with histological parameters of NAFLD in an obese population
Author(s) -
Verrijken A.,
Beckers S.,
Francque S.,
Hilden H.,
Caron S.,
Zegers D.,
Ruppert M.,
Hubens G.,
Marck E.,
Michielsen P.,
Staels B.,
Taskinen M.R.,
Hul W.,
Gaal L.
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20366
Subject(s) - steatohepatitis , insulin resistance , fatty liver , medicine , liver biopsy , steatosis , metabolic syndrome , endocrinology , body mass index , gastroenterology , population , obesity , biopsy , disease , environmental health
Objective Mechanisms explaining the relationship in 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 Overweight and obese 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 Four hundred seventy 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 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.