title: The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritou
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hagihara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D016751:Hepatitis E / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008049:Lipase / Q000235:genetics*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent