title: Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD).
abstract: BACKGROUND
  Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor gamma coactivator 1alpha polymorphism (PPARGC1A) and NAFLD.
  
  
  OBJECTIVE
  We recruited 115 patients with biopsy-proven NAFLD, 65 with NASH and 50 with simple steatosis, and 441 healthy control subjects and investigated 15 SNPs of PPARGC1A.
  
  
  RESULTS
  SNP rs2290602 had the lowest p value in the dominant mode (p = 0.00095), and the odds ratio for NAFLD (95% CI) was 2.73 (1.48 - 5.06). rs2290602 was significantly associated with NAFLD even when the most conservative Bonferroni's correction was applied (p = 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (p = 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (p = 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression of PPARGC1A was lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).
  
  
  CONCLUSIONS
  This is the first study to demonstrate a significant association between genetic variations in PPARGC1A and NAFLD. This finding suggested that PPARGC1A polymorphism and lower expression of PPARGC1A mRNA in the liver are an important genetic contribution to etiology of NAFLD.
authors.affiliation: Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Yokohama, Japan. yoneda@med.yokohama-cu.ac.jp
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: Kunihiro
authors.initials: K
authors.lastname: Hosono
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yoneda
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; D016022:Case-Control Studies; D003199:Computer Systems; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors