A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. (6th June 2013)

• Record Type: Journal Article
• Authors: Verrijken, A.; Beckers, S.; Francque, S.; Hilden, H.; Caron, S.; Zegers, D.; Ruppert, M.; Hubens, G.; Van, E.; Michielsen, P.; Staels, B.; Taskinen, M.‐R.; Van, W.; Van, L.
• Is Part Of: Obesity. Volume 21:Number 10(2013:Oct.)
• Page Start: 2138
• Page End: 2145
• Publication Date: 2013-06-06
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20366
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20366-sec-0001" sec-type="section"> <title>Objective</title> <p>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 (<italic>PNPLA3</italic>) and apolipoprotein C3 (<italic>APOC3</italic>) and metabolic and histological parameters of NAFLD in obese patients.</p> </sec> <sec id="oby20366-sec-0002" sec-type="section"> <title>Design and Methods</title> <p>Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. <italic>APOC3</italic> variant rs2854117 and <italic>PNPLA3</italic> variant rs738409 were genotyped.</p> </sec> <sec id="oby20366-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>PNPLA3</italic> variant. After adjustment for age and body mass index, the <italic>PNPLA3</italic> variant was associated with alanine aminotransferase (<italic>P</italic> < 0.001) and aspartate aminotransferase (<italic>P</italic> < 0.001). The <italic>PNPLA3</italic> variant was associated with more severe features of steatohepatitis: steatosis (<italic>P</italic> < 0.001), lobular inflammation (<italic>P</italic> < 0.001), and ballooning (<italic>P</italic> = 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 <italic>APOC3</italic> variant.</p> </sec> <sec id="oby20366-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>PNPLA3</italic> polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between <italic>APOC3</italic> gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.</p> </sec> </abstract>