Research article

Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD)

Masato Yoneda^{* 1} , Kikuko Hotta^{* 2} , Yuichi Nozaki¹ , Hiroki Endo¹ , Takashi Uchiyama¹ , Hironori Mawatari¹ , Hiroshi Iida¹ , Shingo Kato¹ , Kunihiro Hosono¹ , Koji Fujita¹ , Kyoko Yoneda¹ , Hirokazu Takahashi¹ , Hiroyuki Kirikoshi¹ , Noritoshi Kobayashi¹ , Masahiko Inamori¹ , Yasunobu Abe¹ , Kensuke Kubota¹ , Satoru Saito¹ , Shiro Maeyama³ , Koichiro Wada⁴ and Atsushi Nakajima¹

¹Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Yokohama, Japan

²Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Japan

³Kitakashiwa Rehabilitation Hospital, 265 Kashiwasita, Kashiwa, Japan

⁴Department of Pharmacology, Osaka University, Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, Japan

author email corresponding author email* Contributed equally

BMC Gastroenterology 2008, 8:27doi:10.1186/1471-230X-8-27

Published:	27 June 2008

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 γ coactivator 1α polymorphism (PPARGC1A) and NAFLD.

Aims

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).

Conclusion

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.