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

• Main Authors: Abe Yasunobu, Inamori Masahiko, Kobayashi Noritoshi, Kirikoshi Hiroyuki, Takahashi Hirokazu, Yoneda Kyoko, Fujita Koji, Hosono Kunihiro, Kato Shingo, Iida Hiroshi, Mawatari Hironori, Uchiyama Takashi, Endo Hiroki, Nozaki Yuichi, Hotta Kikuko, Yoneda Masato, Kubota Kensuke, Saito Satoru, Maeyama Shiro, Wada Koichiro, Nakajima Atsushi
• Format: Article
• Language: English
• Published: BMC 2008-06-01
• Series: BMC Gastroenterology
• Online Access: http://www.biomedcentral.com/1471-230X/8/27

<p>Abstract</p> <p>Background</p> <p>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 (<it>PPARGC1A</it>) and NAFLD.</p> <p>Aims</p> <p>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 <it>PPARGC1A</it>.</p> <p>Results</p> <p>SNP rs2290602 had the lowest <it>p </it>value in the dominant mode (<it>p </it>= 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 (<it>p </it>= 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (<it>p </it>= 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (<it>p </it>= 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression of <it>PPARGC1A </it>was lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).</p> <p>Conclusion</p> <p>This is the first study to demonstrate a significant association between genetic variations in <it>PPARGC1A </it>and NAFLD. This finding suggested that <it>PPARGC1A </it>polymorphism and lower expression of <it>PPARGC1A </it>mRNA in the liver are an important genetic contribution to etiology of NAFLD.</p>