title: Influence of inducible nitric oxide synthase polymorphisms in Japanese patients with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD.
  
  
  METHODS
  A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
  
  
  RESULTS
  We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P-value in the allele frequency model (P = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32-0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
  
  
  CONCLUSIONS
  This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.
authors.affiliation: Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masato
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authors.lastname: Yoneda
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Hiroki
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authors.lastname: Endo
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.forename: Seitaro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kunihiro
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authors.lastname: Hosono
authors.forename: Hironori
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authors.lastname: Mawatari
authors.forename: Hiroshi
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authors.lastname: Iida
authors.forename: Koji
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authors.lastname: Fujita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroyuki
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authors.lastname: Kirikoshi
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Masahiko
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authors.lastname: Inamori
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Shiro
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authors.lastname: Maeyama
authors.forename: Koichiro
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authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima