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Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Host genetic factors have been suspected to influence histological liver damage in chronic liver disease. The nonsynonymous single-nucleotide polymorphism rs738409 C > G in the patatin-like phospholipase domain-containing 3 gene (PNPLA3, also known as adiponutrin), encoding the I148 M protein variant, has been identified as a novel genetic marker for hepatic steatosis and fibrosis in nonalcoholic fatty liver disease and alcoholic liver disease. We aimed to determine whether the PNPLA3 rs738409 variant was associated with hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.

Methods

In a cross-sectional study in Japan, we analyzed 276 patients with chronic hepatitis C who underwent liver biopsy. Genotyping for rs738409 was performed using the TaqMan genotyping assay.

Results

The frequencies of the rs738409 CC, CG, and GG genotypes were 32.6, 46.4, and 21.0 %, respectively. Multivariate analysis revealed that the GG genotype was independently associated with the presence of steatosis [odds ratio (OR) 2.58, 95 % confidence interval (CI) 1.37–4.84, p = 0.003], severe necroinflammatory activity (OR 2.16, 95 % CI 1.12–4.16, p = 0.02), and advanced fibrosis (OR 2.10, 95 % CI 1.07–4.11, p = 0.03), after adjustment for age, sex, body mass index, and diabetes.

Conclusions

The PNPLA3 rs738409 variant influences histological liver damage in Japanese patients with chronic hepatitis C. The G allele homozygotes are at higher risk for hepatic steatosis, severe necroinflammation, and advanced fibrosis.

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Acknowledgments

This work was supported by a grant from the Ministry of Health, Labour and Welfare of Japan (H20-hepatitis-008 to Takeshi Okanoue, H24-hepatitis-general-006 to Takeshi Okanoue).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Kohichiroh Yasui, Hironori Mitsuyoshi & Yoshito Itoh

  2. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Takahisa Kawaguchi & Fumihiko Matsuda

  3. Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, 564-0013, Japan

    Toshihide Shima, Kojiro Seki, Rei Sendo, Masayuki Mizuno & Takeshi Okanoue

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  1. Kohichiroh Yasui
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  2. Takahisa Kawaguchi
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Correspondence to Takeshi Okanoue.

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Yasui, K., Kawaguchi, T., Shima, T. et al. Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C. J Gastroenterol 50, 887–893 (2015). https://doi.org/10.1007/s00535-014-1018-z

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  • DOI: https://doi.org/10.1007/s00535-014-1018-z

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