title: PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients.
abstract: OBJECTIVE
  To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients.
  
  
  METHODS
  Two hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment.
  
  
  RESULTS
  PNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03-1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03-1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97-4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13-9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07-1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15-5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90-3.71); p = 0.0936) as the factors independently associated with HCC.
  
  
  CONCLUSIONS
  PNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakaoka
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Senju
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawabe
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nitta
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Michihito
authors.initials: M
authors.lastname: Murao
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimazaki
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kan
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takagawa
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohki
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kurashita
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takamura
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Faculty of Medical Technology, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192 Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Ichino
authors.affiliation: Faculty of Medical Technology, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192 Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Osakabe
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
keywords: Chronic hepatitis C; Cirrhosis; HCC; HCV; PNPLA3; SNP