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Moon S, Chung GE, Joo SK, et al. A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2021;doi: 10.1016/j.cgh.2021.04.038.
Moon, S., Chung, G. E., Joo, S. K., Park, J. H., Chang, M. S., Yoon, J. W., Koo, B. K., & Kim, W. (2021). A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, . https://doi.org/10.1016/j.cgh.2021.04.038
Moon, Seoil, et al. "A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease." Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association vol. (2021). doi: https://doi.org/10.1016/j.cgh.2021.04.038
Moon S, Chung GE, Joo SK, Park JH, Chang MS, Yoon JW, Koo BK, Kim W. A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2021 Apr 24; doi: 10.1016/j.cgh.2021.04.038. Epub 2021 Apr 24. PMID: 33905771.
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Clin Gastroenterol Hepatol. 2021 Apr 24; doi: 10.1016/j.cgh.2021.04.038. Epub 2021 Apr 24.

A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

Seoil Moon, Goh Eun Chung, Sae Kyung Joo, Jeong Hwan Park, Mee Soo Chang, Ji Won Yoon, Bo Kyung Koo, Won Kim

Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium.
  2. Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium.
  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium.
  4. Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium.
  5. Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium. Electronic address: [email protected].
  6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea; On behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium. Electronic address: [email protected].

PMID: 33905771 DOI: 10.1016/j.cgh.2021.04.038

Abstract

BACKGROUND AND AIMS: We investigated the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genotype and the risk of diabetes mellitus (DM) using a biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) cohort and a longitudinal observational cohort.

METHODS: Associations between genotypes and the prevalence of DM were evaluated with stratification according to the histological severity of NAFLD in the Boramae cohort (n = 706). A longitudinal cohort consisting of nondiabetic individuals with ≥2 health checkups was then selected to investigate the risk of incident DM according to the genotype (the GENIE cohort; n = 4998).

RESULTS: Among subjects with NAFLD in the Boramae cohort, the G allele was independently associated with a lower prevalence of DM in both NAFL (odds ratio [OR] per 1 allele, 0.66; 95% confidence interval [CI], 0.46-0.97) and nonalcoholic steatohepatitis (OR per 1 allele, 0.59; 95% CI, 0.38-0.92). This result was replicated in the longitudinal GENIE cohort. The G allele was associated with a lower risk of incident DM during the median follow-up of 60 months in subjects with NAFLD (hazard ratio, 0.65; 95% CI, 0.45-0.93). In contrast, G allele carriers without NAFLD showed higher odds for DM in the context of the Boramae cohort (OR, 2.44; 95% CI, 1.00-5.95).

CONCLUSIONS: These findings clarify conflicting results regarding the association between the PNPLA3 rs738409 genotype and the risk of DM, demonstrating a clear difference between subjects with and without NAFLD; this difference might be explained by the low metabolic risk in genetic NAFLD.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Keywords: Diabetes Mellitus; Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis; PNPLA3

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