PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease.

Research paper by Jiayun J Shen, Grace Lai-Hung GL Wong, Henry Lik-Yuen HL Chan, Ruth Suk-Mei RS Chan, Hoi-Yun HY Chan, Winnie Chiu-Wing WC Chu, Bernice Ho-Ki BH Cheung, David Ka-Wai DK Yeung, Liz Sin LS Li, Mandy Man-Mei MM Sea, Jean J Woo, Vincent Wai-Sun VW Wong

Indexed on: 22 Jul '14Published on: 22 Jul '14Published in: Journal of Gastroenterology and Hepatology


Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients.This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy.One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group.Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.

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