<scp>PNPLA</scp>3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease

Shen, Jiayun; Wong, Grace Lai–Hung; Chan, Henry Lik‐Yuen; Chan, Randolph C. H.; Chan, Hoi–Yun; Chu, Winnie C.W.; Cheung, Bernice; Yeung, David W. K.; Li, Liz Sin; Sea, Mandy Man-Mei; Woo, Jean; Wong, Vincent Wai‐Sun

doi:10.1111/jgh.12656

Cited by 138 publications

(105 citation statements)

References 25 publications

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“…KD have also been associated with a higher decrease in liver volume compared with a standard hypocaloric diet, probably due to the depletion of liver glycogen [59]. Finally, the response to KD may be influenced by genetic predisposition to NAFLD, as shown by two studies with a better response to KD for patients with variants of the PNPLA3 gene [60,61]. When fed a KD, subjects with PNPLA3 variants had a lower liver fat content than controls.…”

Section: Resultsmentioning

confidence: 99%

Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

2017

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The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence.

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Section: Resultsmentioning

confidence: 99%

Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

2017

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“…Nonetheless, our previous study has shown that lifestyle modifi cation despite modest weight reduction is helpful for the treatment of NAFLD ( 33 ). Furthermore, carriers of the PNPLA3 G allele experience greater improvement in liver fat aft er lifestyle modifi cation ( 34 ). As most non-obese NAFLD patients are carriers of the G allele, these patients would likely benefi t from lifestyle modifi cation.…”

Section: Non-obese Fatty Livermentioning

confidence: 97%

Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy

Wei

Leung

Loong

et al. 2015

American Journal of Gastroenterology

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275

237

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“…Interestingly, children carrying the PNPLA3 prosteatotic allele seemed to benefit the most from the weight loss [16] . A recent analysis of 154 adult patients in whom hepatic fat contents were quantified with proton-magnetic resonance spectroscopy also showed that individuals carrying the PNPLA3 risk allele might benefit the most from lifestyle changes [29] . The recent analysis of the WELCOME trial, a 15-18 month intervention with omega-3 fatty acids in patients with NAFLD demonstrated that carriage of the PNPLA3 p.148MM genotype influenced the change in liver fat and docosahexaenoic acid (DHA) tissue enrichment [23] .…”

Section: Discussionmentioning

confidence: 99%

Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3 p.I148M and TM6SF2 p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study

Krawczyk

Stachowska²,

Milkiewicz³

et al. 2016

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Background: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent risk factors for non-alcoholic fatty liver disease (NAFLD). In this study, we assessed the effects of caloric restriction on liver phenotypes in NAFLD patients in relation to the PNPLA3 and TM6SF2 genotypes. Methods: We genotyped both variants in 143 individuals with NAFLD (55 females, age 18-74 years) and 180 controls (85 females, age 33-66 years). Liver steatosis was assessed using the ultrasound-based Hamaguchi score. A 4-month dietetic intervention, consisting of restriction of daily caloric intake without changes in physical activity, was performed. Results: Both PNPLA3 (p = 0.002) and TM6SF2 (p = 0.041) variants were associated with NAFLD before intervention. Overall, 88 patients completed the intervention, which led to a significant decrease of steatosis, ALT activities, body mass index, hip and waist circumferences, and waist-hip ratio (all p < 0.0001). Hepatic steatosis and anthropometric traits improved significantly (p < 0.05) in carriers of either PNPLA3 or TM6SF2 risk genotype. The improvement of phenotypic traits, apart from WHR (p = 0.02), was not modified by the presence of PNPLA3 or TM6SF2 variants. Conclusions: The PNPLA3 and TM6SF2 polymorphisms are associated with NAFLD assessed by the Hamaguchi score. Neither PNPLA3 nor TM6SF2 risk alleles impair the response to dietetic intervention in NAFLD.

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

Abstract: 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.

Cited by 138 publications

References 25 publications

Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy

Reduction of Caloric Intake Might Override the Prosteatotic Effects of the <b><i>PNPLA3</i></b> p.I148M and <b><i>TM6SF2</i></b> p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study

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