title: Association between angiotensin II type 1 receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries. Genetic factors are important for the development of NAFLD, as well as environmental factors. Recently an angiotensin II type 1 receptor (AGTR1) has been recognized as important in the aetiology of fibrosis in the liver.
  
  
  OBJECTIVE
  In this study we investigated the association between angiotensin II type 1 receptor gene polymorphism (ATGR1) and NAFLD.
  
  
  METHODS
  One hundred and sixty-seven NAFLD patients [106 with nonalcoholic steatohepatitis (NASH) and 61 with simple steatosis] with a positive diagnosis by liver biopsy and 435 healthy control subjects were recruited in this study.
  
  
  RESULTS
  We investigated 12 single nucleotide polymorphisms (SNPs) of the ATGR1 gene, among which rs3772622 showed the lowest P-value of allele frequency model (P=0.0000012) with an odds ratio (95% confidence interval) of 1.95 (1.49-2.55). Five SNPs (rs3772622, rs3772633, rs2276736, rs3772630 and rs3772627) were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs3772622 and another four SNPs (rs3772633, rs2276736, rs3772630 and rs3772627) were in the same block. We investigated the association between rs3772622 genotypes and the fibrosis index. The results of the analysis revealed an additive increase of the fibrosis index in the patients with the A allele of rs3772622.
  
  
  CONCLUSIONS
  This is the first report to demonstrate the genetic variations in ATGR1 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 City University Hospital, Yokohama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endo
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iida
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inamori
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeyama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D044140:Receptor, Angiotensin, Type 1