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Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.
J Gastroenterol. 2015 Aug; 50(8):887-93.JG

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.

Authors+Show Affiliations

Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25543233

Citation

Yasui, Kohichiroh, et al. "Effect of PNPLA3 Rs738409 Variant (I148 M) On Hepatic Steatosis, Necroinflammation, and Fibrosis in Japanese Patients With Chronic Hepatitis C." Journal of Gastroenterology, vol. 50, no. 8, 2015, pp. 887-93.
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. 2015;50(8):887-93.
Yasui, K., Kawaguchi, T., Shima, T., Mitsuyoshi, H., Seki, K., Sendo, R., Mizuno, M., Itoh, Y., Matsuda, F., & Okanoue, T. (2015). Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C. Journal of Gastroenterology, 50(8), 887-93. https://doi.org/10.1007/s00535-014-1018-z
Yasui K, et al. Effect of PNPLA3 Rs738409 Variant (I148 M) On Hepatic Steatosis, Necroinflammation, and Fibrosis in Japanese Patients With Chronic Hepatitis C. J Gastroenterol. 2015;50(8):887-93. PubMed PMID: 25543233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C. AU - Yasui,Kohichiroh, AU - Kawaguchi,Takahisa, AU - Shima,Toshihide, AU - Mitsuyoshi,Hironori, AU - Seki,Kojiro, AU - Sendo,Rei, AU - Mizuno,Masayuki, AU - Itoh,Yoshito, AU - Matsuda,Fumihiko, AU - Okanoue,Takeshi, Y1 - 2014/11/26/ PY - 2014/08/27/received PY - 2014/11/09/accepted PY - 2014/12/29/entrez PY - 2014/12/30/pubmed PY - 2016/5/3/medline SP - 887 EP - 93 JF - Journal of gastroenterology JO - J. Gastroenterol. VL - 50 IS - 8 N2 - 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. SN - 1435-5922 UR - https://www.unboundmedicine.com/medline/citation/25543233/Effect_of_PNPLA3_rs738409_variant__I148_M__on_hepatic_steatosis_necroinflammation_and_fibrosis_in_Japanese_patients_with_chronic_hepatitis_C_ L2 - https://dx.doi.org/10.1007/s00535-014-1018-z DB - PRIME DP - Unbound Medicine ER -