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The PNPLA3 I148M polymorphism is associated with insulin resistance and nonalcoholic fatty liver disease in a normoglycaemic population
Author(s) -
Wang ChihWen,
Lin HsingYi,
Shin ShyiJang,
Yu MingLung,
Lin ZuYau,
Dai ChiaYen,
Huang JeeFu,
Chen ShinnCherng,
Li Steven ShoeiLung,
Chuang WanLong
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02526.x
Subject(s) - insulin resistance , nonalcoholic fatty liver disease , medicine , odds ratio , genotype , endocrinology , population , fatty liver , biology , gastroenterology , insulin , disease , genetics , gene , environmental health
Background and Aims: The adiponutrin/patatin‐like phospholipase‐3 ( PNPLA3 ) I148M polymorphism has recently been found to contribute to differences in hepatic lipid content. Nonalcoholic fatty liver disease (NAFLD) has recently been considered a hepatic component of insulin resistance and a risk factor in the emergence of type 2 diabetes. However, whether there is an association between PNPLA3 I148M and insulin resistance and NAFLD in a normoglycaemic population is still unknown.Methods: This study enrolled 156 normoglycaemic individuals with NAFLD and 723 controls. All participants received complete biochemical and clinical workups including liver ultrasonography. They were then genotyped for the PNPLA3 I148M polymorphism.Results: We found significant differences in the genotype and the dominant model of the PNPLA3 I148M polymorphism between the NAFLD groups and the controls ( P =0.018 and P =0.01 respectively). Furthermore, there was a dose effect of the PNPLA3 I148M genotype, in that CG heterozygotes had a risk of NAFLD between CC and GG homozygotes [adjusted odds ratio (OR)=2.03, 95% confidence interval (CI)=1.23–3.375 for the GG genotype and adjusted OR=1.55, 95% CI=1.02–2.35 for the CG genotype]. The dominant model of the PNPLA3 I148M polymorphism showed higher waist circumference, fasting insulin, Homeostasis Model Assessment (HOMA‐IR), alanine aminotransferase concentrations and ferritin level. Multivariate analysis showed the PNPLA3 I148M polymorphism to be independently and significantly associated with NAFLD in our normoglycaemic participants.Conclusion: This study reports an association between the PNPLA3‐I148M polymorphism and insulin resistance and NAFLD in a normoglycaemic population.