TY - JOUR
T1 - The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus
AU - Ueyama, Misuzu
AU - Nishida, Nao
AU - Korenaga, Masaaki
AU - Korenaga, Keiko
AU - Kumagai, Erina
AU - Yanai, Hidekatsu
AU - Adachi, Hiroki
AU - Katsuyama, Hisayuki
AU - Moriyama, Sumie
AU - Hamasaki, Hidetaka
AU - Sako, Akahito
AU - Sugiyama, Masaya
AU - Aoki, Yoshihiko
AU - Imamura, Masatoshi
AU - Murata, Kazumoto
AU - Masaki, Naohiko
AU - Kawaguchi, Takumi
AU - Torimura, Takuji
AU - Hyogo, Hideyuki
AU - Aikata, Hiroshi
AU - Ito, Kiyoaki
AU - Sumida, Yoshio
AU - Kanazawa, Akio
AU - Watada, Hirotaka
AU - Okamoto, Koji
AU - Honda, Kenjiro
AU - Kon, Kazuyoshi
AU - Kanto, Tatsuya
AU - Mizokami, Masashi
AU - Watanabe, Sumio
N1 - Funding Information:
We thank Ms. Yoriko Mawatari, Ms. Mayumi Ishii, Ms. Takayo Tsuchiura, Ms. Kozue Sugimoto, and Ms. Noriko Ota for their technical support. This study was supported by grants (25-202, 26-206) from the National Center for Global Health and Medicine in Japan and the Ministry of Education, Culture, Sports, Science, and Technology (No. 25461019) and by a research award from the Liver Forum in Kyoto; it was also supported in part by the Ministry of Health, Labour, and Welfare of Japan.
Publisher Copyright:
© 2015, Springer Japan.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Hepatocellular carcinoma
KW - JAZF1
KW - PNPLA3
KW - Type 2 diabetes mellitus
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U2 - 10.1007/s00535-015-1116-6
DO - 10.1007/s00535-015-1116-6
M3 - Article
C2 - 26337813
AN - SCOPUS:84940705917
SN - 0944-1174
VL - 51
SP - 370
EP - 379
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
IS - 4
ER -
