The C-681G Polymorphism of the PPAR-γ Gene Is Associated with Susceptibility to Non-Alcoholic Fatty Liver Disease

The C-681G Polymorphism of the PPAR-γ Gene Is Associated with Susceptibility to Non-Alcoholic Fatty Liver Disease

CHUANG-YU CAO,¹ YU-YUAN LI,¹ YONG-JIAN ZHOU,¹ YU-QIANG NIE¹ and YU-JUI YVONNE WAN²

¹Department of Gastroenterology and Hepatology, Guangzhou Institute of Clinical Medicine, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, P.R. China
²Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, USA

Non-alcoholic fatty liver disease (NAFLD) is defined as excessive accumulation of fatty acid in the liver, a common disease in the world. The research of single nucleotide polymorphisms (SNPs) provides a new approach for managing NAFLD. SNPs may increase or decrease the functions of the target genes and their encoding proteins. Peroxisome proliferator-activated receptor (PPAR) plays a key role in modulating metabolism of hepatic triglycerides and consequently magnitude of NAFLD. In this study, we investigated the effect of three SNPs in the PPAR-γ gene i.e. rs10865710 (C-681G), rs7649970 (C-689T) and rs1801282 (C34G, also termed Pro12Ala) on susceptibility to NAFLD. The participants were selected from our epidemiological survey. Totally 169 participants were enrolled in NAFLD group, and 699 healthy subjects were included as controls. PCR-RFLP was applied to detect the SNPs. The G allele frequency of rs10865710 in NAFLD group (41.1%) was significantly higher than that (34.8%) in controls (p = 0.03). Differences in other two loci (rs7649970 and rs1801282) were not statistically significant between the two groups (p > 0.05). This result was confirmed by haplotype analysis. The GCC haplotype (a set of 3 adjacent SNPs in linkage disequilibrium, corresponding to the three alleles of above polymorphisms in order) was a risk factor for the susceptibility to NAFLD (p = 0.03). This study has revealed that the G allele of rs10865710 in the PPAR-γ gene is associated with the increased susceptibility to NAFLD. Our findings may provide novel diagnostic biomarkers and therapeutic targets for NAFLD.

keywords —— gene; insulin resistance; non-alcoholic fatty liver disease; peroxisome proliferator-activated receptor-γ; polymorphism

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Tohoku J. Exp. Med., 2012, 227, 253-262

Correspondence: Yu-Yuan Li, Department of Gastroenterology and Hepatology, Guangzhou Institute of Clinical Medicine, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, 510180, P.R. China.

e-mail: liyyliyy@tom.com