I148M variant of PNPLA3 increases the susceptibility to non‐alcoholic fatty liver disease caused by obesity and metabolic disorders

Xia, Mingfeng; Ling, Yan; Bian, Hua; Hao, Lin; Yan, Hongmei; Chang, Xinxia; Li, X.-M.; Ma, Hui; Wang, D.; Zhang, L.-S.; Wang, S.-S.; Wu, Bingjie; He, Wenzhuan; Zhao, Na

doi:10.1111/apt.13521

Cited by 31 publications

(30 citation statements)

References 52 publications

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“…the I148M variant in PNPLA3 [27] and the E167K variant in TM6SF2 [28]. The frequency of the I148M gene variant has been reported to be 37.0% [29] and 38.0% [30] in Chinese and 37.9% in Europid subjects [31, 32]. The frequency of E167K gene variant has been reported to be 6.7% in the Chinese [33] and about 7% in Europid subjects [27,34,35].…”

Section: Discussionmentioning

confidence: 99%

Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease

et al. 2016

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ObjectivesPresence of non-alcoholic fatty liver disease (NAFLD) can predict risks for diabetes, cardiovascular disease and advanced liver disease in the general population. We aimed to establish a non-invasive score for prediction of NAFLD in Han Chinese, the largest ethnic group in the world, and detect whether ethnicity influences the accuracy of such a score.MethodsLiver fat content (LFAT) was measured by quantitative ultrasound in 3548 subjects in the Shanghai Changfeng Community and a Chinese score was created using multivariate logistic regression analyses. This new score was internally validated in Chinese and externally in Finns. Its diagnostic performance was compared to the NAFLD liver fat score, fatty liver index (FLI) and hepatic steatosis index (HSI) developed in Finns, Italians and Koreans. We also analyzed how obesity related to LFAT measured by 1H-MRS in 79 Finns and 118 Chinese with type 2 diabetes (T2D).ResultsThe metabolic syndrome and T2D, fasting serum insulin, body mass index (BMI) and AST/ALT ratio were independent predictors of NAFLD in Chinese. The AUROC in the Chinese validation cohort was 0.76 (0.73–0.78) and in Finns 0.73 (0.68–0.78) (p<0.0001). 43%, 27%, 32% and 42% of Chinese had NAFLD when determined by the Chinese score, NAFLD liver fat score (p<0.001 vs. Chinese score), FLI (p<0.001) and HSI (NS). For any given BMI and waist circumference, the Chinese had a markedly higher LFAT than the Finns.ConclusionThe predictors of NAFLD in Han Chinese are as in Europids but the Chinese have more LFAT for any given degree of obesity than Europids. Ethnicity needs to be considered when NAFLD is predicted using risk scores.

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Section: Discussionmentioning

confidence: 99%

Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease

et al. 2016

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“…[10] Numerous studies have shown that PNPLA3 may be the most important gene for the occurrence for NAFLD, in particular, a nonsynonymous sequence variation (rs738409 C > G, I148M) in PNPLA3 has been identified to be strongly associated not only with steatosis but also with clinically relevant factors and the progression of NAFLD. [11,12] A GWAS from Kawaguchi et al [8] had revealed several SNPs, including rs2896019 and rs3810622 in the PNPLA3 gene, were associated with the histological classifications of NAFLD in the Japanese population. Kitamoto et al [13] also discovered that these 2 SNPs were associated with the progression of simple steatosis to NASH and the development of NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Association of patatin-like phospholipase domain-containing protein 3 gene polymorphisms with susceptibility of nonalcoholic fatty liver disease in a Han Chinese population

Song

Xiao²,

Wang³

et al. 2016

Medicine

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“…Participants The Shanghai Changfeng Community Study recruited 4300 Chinese community residents (1652 men, 2648 women) aged >45 years from May 2010 to December 2012. Participants with medical records or self-reports of previous viral hepatitis, excessive alcohol consumption and chronic liver diseases other than NAFLD were excluded [14]. In the current study, we report the first-round follow-up results of the Changfeng large-scale community study.…”

Section: Methodsmentioning

confidence: 99%

“…In one largescale cohort study in Germany, the PNPLA3 rs738409 G variant was found to be associated with increased liver diseaseassociated mortality but reduced coronary heart diseaseassociated mortality [12]. Adiposity can amplify the effect of the PNPLA3 rs738409 C>G variant on liver fat accumulation according to recent studies [13][14][15]. Weight gain is the most important risk factor for both NAFLD [16] and type 2 diabetes [17].…”

Section: Introductionmentioning

confidence: 99%

The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes

et al. 2019

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Aims/hypothesis The rs738409 C>G variant of the patatin-like phospholipase domain containing 3 gene (PNPLA3) increases the risk of non-alcoholic fatty liver disease (NAFLD) with no predisposition for insulin resistance. In this study, we aimed to investigate the influence of PNPLA3 polymorphisms on liver fat content (LFC) and glucose metabolic variables, and the associations between these, during the natural course of body weight changes in a Chinese adult cohort. Methods The LFC, measured using a quantitative ultrasound method, was prospectively monitored in 2189 middleaged and elderly adults from the Shanghai Changfeng Study, together with changes in body weight and metabolic variables. General linear models were used to detect interactive effects between the PNPLA3 rs738409 genotype and 4 year changes in body weight on liver steatosis and glucose metabolism. Results The PNPLA3 homozygous GG genotype dissociated the changes in the LFC and OGTT 2 h post-load blood glucose (PBG) in relation to 4 year changes in body weight. PNPLA3 GG genotype carriers showed greater increases in the LFC and serum alanine aminotransferase (ALT) but lower PBG elevation and incident diabetes than PNPLA3 wild-type (CC) genotype carriers exhibiting the same degree of body weight increase. The interactions between the PNPLA3 genotype and changes in body weight on the LFC (false discovery rate [FDR]-adjusted p interaction = 0.044) and ALT (FDR-adjusted p interaction = 0.044) were significant. Subgroup analyses showed that the effect of the PNPLA3 GG genotype on changes in the LFC and PBG was only observed in metabolically unhealthy participants with insulin resistance or abdominal obesity. Conclusions/interpretation The PNPLA3 GG genotype interacted with changes in body weight to aggravate liver steatosis but reduced the risk of incident type 2 diabetes in metabolically unhealthy participants.

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I148M variant of PNPLA3 increases the susceptibility to non‐alcoholic fatty liver disease caused by obesity and metabolic disorders

Cited by 31 publications

References 52 publications

Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease

Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease

Association of patatin-like phospholipase domain-containing protein 3 gene polymorphisms with susceptibility of nonalcoholic fatty liver disease in a Han Chinese population

The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes

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