Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD).
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.
Yoneda
Masato
M
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Yokohama, Japan. yoneda@med.yokohama-cu.ac.jp
Hotta
Kikuko
K
Nozaki
Yuichi
Y
Endo
Hiroki
H
Uchiyama
Takashi
T
Mawatari
Hironori
H
Iida
Hiroshi
H
Kato
Shingo
S
Hosono
Kunihiro
K
Fujita
Koji
K
Yoneda
Kyoko
K
Takahashi
Hirokazu
H
Kirikoshi
Hiroyuki
H
Kobayashi
Noritoshi
N
Inamori
Masahiko
M
Abe
Yasunobu
Y
Kubota
Kensuke
K
Saito
Satoru
S
Maeyama
Shiro
S
Wada
Koichiro
K
Nakajima
Atsushi
A
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*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors