The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus

Misuzu Ueyama, Nao Nishida, Masaaki Korenaga, Keiko Korenaga, Erina Kumagai, Hidekatsu Yanai, Hiroki Adachi, Hisayuki Katsuyama, Sumie Moriyama, Hidetaka Hamasaki, Akahito Sako, Masaya Sugiyama, Yoshihiko Aoki, Masatoshi Imamura, Kazumoto Murata, Naohiko Masaki, Takumi Kawaguchi, Takuji Torimura, Hideyuki Hyogo, Hiroshi AikataKiyoaki Ito, Yoshio Sumida, Akio Kanazawa, Hirotaka Watada, Koji Okamoto, Kenjiro Honda, Kazuyoshi Kon, Tatsuya Kanto, Masashi Mizokami, Sumio Watanabe

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Background: Type 2 diabetes mellitus (T2DM) is an established independent risk factor for hepatocellular carcinoma (HCC). T2DM is associated with non-alcoholic steatohepatitis (NASH), which is a major cause of non-HBV and non-HCV-related HCC; nevertheless, it has been difficult to identify those patients with T2DM who have a high risk of developing HCC. The aim of this study was to identify genetic determinants that predispose T2DM patients to HCC by genotyping T2DM susceptibility loci and PNPLA3. Methods: We recruited 389 patients with T2DM who satisfied the following three criteria: negative for HBs-Ag and anti-HCV Ab, alcohol intake <60 g/day, and history of T2DM >10 years. These patients were divided into two groups: T2DM patients with HCC (DM–HCC, n = 59) or those without HCC (DM–non-HCC, n = 330). We genotyped 51 single-nucleotide polymorphisms (SNPs) previously reported as T2DM or NASH susceptibility loci (PNPLA3) compared between the DM-HCC and DM-non-HCC groups with regard to allele frequencies at each SNP. Results: The SNP rs738409 located in PNPLA3 was the greatest risk factor associated with HCC. The frequency of the PNPLA3 G allele was significantly higher among DM–HCC individuals than DM–non-HCC individuals (OR 2.53, p = 1.05 × 10−5). Among individuals homozygous for the PNPLA3 G allele (n = 115), the frequency of the JAZF1 rs864745 G allele was significantly higher among DM–HCC individuals than DM–non-HCC individuals (OR 3.44, p = 0.0002). Conclusions: PNPLA3 and JAZF1 were associated with non-HBV and non-HCV-related HCC development among Japanese patients with T2DM.

Original languageEnglish
Pages (from-to)370-379
Number of pages10
JournalJournal of gastroenterology
Volume51
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • JAZF1
  • PNPLA3
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Gastroenterology

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