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The PNPLA3 I148M polymorphism is associated with insulin resistance and nonalcoholic fatty liver disease in a normoglycaemic population

Authors

  • Chih-Wen Wang,

    1. Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
    2. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
    3. Department of Internal Medicine, Chi-Shan Hospital, Department of Health, Executive Yuan, ROC
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    • *Contributed equally.

  • Hsing-Yi Lin,

    1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
    2. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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    • *Contributed equally.

  • Shyi-Jang Shin,

    1. Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Ming-Lung Yu,

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
    2. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Zu-Yau Lin,

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Chia-Yen Dai,

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Jee-Fu Huang,

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Shinn-Cherng Chen,

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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  • Steven Shoei-Lung Li,

    1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
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  • Wan-Long Chuang

    1. Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
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Wan-Long Chuang, MD, PhD, Department of Internal Medicine, Division of Hepatobiliary Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
Tel: +886 7 3121101, ext 7476
Fax: +886 7 3122810
e-mail: 960384@ms.kmuh.org.tw

Abstract

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.

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