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The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases.

Methods

We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC).

Results

NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and <0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028).

Conclusions

The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients.

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Abbreviations

AFP:

Alpha-fetoprotein

ALD:

Alcoholic liver disease

APRI:

Aspartate aminotransferase to platelet ratio index

BMI:

Body mass index

DCP:

Des-gamma-carboxy prothrombin

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

NAFLD:

Non-alcoholic fatty liver disease

NBNC:

Non-B non-C

PNPLA3:

Patatin-like phospholipase domain-containing protein 3

SNP:

Single nucleotide polymorphism

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Acknowledgments

This work was supported in part by the research program of intractable disease provided by the Ministry of Health, Labor, and Welfare of Japan, and by a grant-in-aid (22590733) for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to Y. I.).

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Yasuto Takeuchi, Fusao Ikeda, Yuki Moritou, Hiroaki Hagihara, Tetsuya Yasunaka, Kenji Kuwaki, Yasuhiro Miyake, Hideki Ohnishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso & Kazuhide Yamamoto

  2. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Fusao Ikeda, Yasuhiro Miyake, Hideki Ohnishi, Kazuhiro Nouso & Kazuhide Yamamoto

  3. Health and Environment Center, Okayama University, Okayama, Japan

    Yoshiaki Iwasaki

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  1. Yasuto Takeuchi
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  2. Fusao Ikeda
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Correspondence to Fusao Ikeda.

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Takeuchi, Y., Ikeda, F., Moritou, Y. et al. The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis . J Gastroenterol 48, 405–412 (2013). https://doi.org/10.1007/s00535-012-0647-3

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  • DOI: https://doi.org/10.1007/s00535-012-0647-3

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