Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection.

Abstract

BACKGROUND & AIMS:

Genetic variants of patatin-like phospholipase domain-containing 3 (PNPLA3) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis.

METHODS:

The PNPLA3 genetic polymorphism at rs738409 was verified in 1077 biopsy-proven CHC patients. Other clinical variables, including diabetes status, were analysed for factors associated with bridging fibrosis.

RESULTS:

Patients with advanced liver fibrosis had higher proportions of the GG genotype (14.5% vs. 10.4%, p=0.06 in recessive model) and GG/GC genotype carriage (64.0% vs. 56.8%, p=0.03 in dominant model). Stepwise logistic regression analysis revealed that factors predictive of advanced liver fibrosis included age (odds ratio [OR]: 1.02, 95% confidence intervals [CI]: 1.008-1.037, p=0.002), diabetes (OR: 1.81, CI: 1.236-2.653, p=0.002), α-fetoprotein (OR: 1.006, CI: 1.001-1.01, p=0.01), platelet counts (OR: 1.009, CI: 1.006-1.012, p<0.001), and PNPLA3 rs738409 CG/GG genotype (OR: 1.34, CI: 1.006-1.785, p=0.046). When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients. The PNPLA3 gene was the most important predictive factor of bridging fibrosis in diabetic patients, using the recessive model (OR: 4.53, CI: 1.356-15.106, p=0.014) or the dominant model (OR: 2.20, CI: 1.026-4.734, p=0.04). Compared to non-diabetic patients, patients with the diabetes/GG genotype were more likely to have advanced liver fibrosis (OR: 8.79, CI: 2.889-26.719, p<0.001), followed by those with diabetes/non-GG genotype (OR: 1.55, CI: 1.048-2.286, p=0.03).

CONCLUSIONS:

The effect of PNPLA3 genetic variants in HCV-related advanced liver fibrosis was enhanced in diabetic patients. The strong genetic-environmental interaction contributed to the high risk of advanced liver disease in CHC patients.

• Authors: Chung-Feng Huang, Chia-Yen Dai, Ming-Lun Yeh, Ching-I Huang, Chi-Ming Tai, Meng-Hsuan Hsieh, Po-Cheng Liang, Yi-Hung Lin, Ming-Yen Hsieh, Hua-Ling Yang, Jee-Fu Huang, Zu-Yau Lin, Shinn-Cherng Chen, Ming-Lung Yu, Wan-Long Chuang
• Journal: Journal of hepatology (J Hepatol) Vol. 62 Issue 3 Pg. 512-8 (Mar 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25457210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Membrane Proteins
• Lipase
• adiponutrin, human

Topics

• Adult
• Aged
• Cohort Studies
• Diabetes Complications (genetics, pathology)
• Female
• Genes, Dominant
• Genes, Recessive
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetic Variation
• Genotype
• Hepatitis C, Chronic (complications, genetics, pathology)
• Humans
• Lipase (genetics)
• Liver Cirrhosis (complications, genetics, pathology)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Models, Genetic
• Polymorphism, Single Nucleotide
• Retrospective Studies
• Risk Factors