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Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection.
J Hepatol. 2015 Mar; 62(3):512-8.JH

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+Show Affiliations

Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25457210

Citation

Huang, Chung-Feng, et al. "Association of Diabetes and PNPLA3 Genetic Variants With Disease Severity of Patients With Chronic Hepatitis C Virus Infection." Journal of Hepatology, vol. 62, no. 3, 2015, pp. 512-8.
Huang CF, Dai CY, Yeh ML, et al. Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection. J Hepatol. 2015;62(3):512-8.
Huang, C. F., Dai, C. Y., Yeh, M. L., Huang, C. I., Tai, C. M., Hsieh, M. H., Liang, P. C., Lin, Y. H., Hsieh, M. Y., Yang, H. L., Huang, J. F., Lin, Z. Y., Chen, S. C., Yu, M. L., & Chuang, W. L. (2015). Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection. Journal of Hepatology, 62(3), 512-8. https://doi.org/10.1016/j.jhep.2014.10.011
Huang CF, et al. Association of Diabetes and PNPLA3 Genetic Variants With Disease Severity of Patients With Chronic Hepatitis C Virus Infection. J Hepatol. 2015;62(3):512-8. PubMed PMID: 25457210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection. AU - Huang,Chung-Feng, AU - Dai,Chia-Yen, AU - Yeh,Ming-Lun, AU - Huang,Ching-I, AU - Tai,Chi-Ming, AU - Hsieh,Meng-Hsuan, AU - Liang,Po-Cheng, AU - Lin,Yi-Hung, AU - Hsieh,Ming-Yen, AU - Yang,Hua-Ling, AU - Huang,Jee-Fu, AU - Lin,Zu-Yau, AU - Chen,Shinn-Cherng, AU - Yu,Ming-Lung, AU - Chuang,Wan-Long, Y1 - 2014/10/20/ PY - 2014/06/03/received PY - 2014/10/06/revised PY - 2014/10/08/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/12/15/medline KW - CHC KW - DM KW - HCV KW - Liver fibrosis KW - PNPLA3 KW - SNP SP - 512 EP - 8 JF - Journal of hepatology JO - J. Hepatol. VL - 62 IS - 3 N2 - 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. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/25457210/Association_of_diabetes_and_PNPLA3_genetic_variants_with_disease_severity_of_patients_with_chronic_hepatitis_C_virus_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(14)00740-5 DB - PRIME DP - Unbound Medicine ER -