Effect of peroxisome proliferator-activated receptors-gamma and co-activator-1alpha genetic polymorphisms on plasma adiponectin levels and susceptibility of non-alcoholic fatty liver disease in Chinese people.
OBJECTIVE
Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) and its co-activator-1alpha (PGC-1alpha) are involved in the regulation of lipid and glucose metabolisms. This study aimed to investigate the genetic polymorphisms of PPAR-gamma and PGC-1alpha in Chinese people and their influence on plasma adiponectin levels and non-alcoholic fatty liver disease (NAFLD) susceptibility.


METHODS
Ninety-six patients with NAFLD and 96 healthy controls were included. The single nucleotide polymorphisms (SNPs) of C161T PPAR-gammaand Gly482Ser PGC-1alpha genes were analysed by polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
The CC, CT and TT genotypic distributions of the NAFLD group were significantly different from those of controls (55.2, 39.6, 5.2 vs. 74.0, 25.0, 1.0%; P=0.015). The allelic frequencies of C and T were also different between the two groups (P=0.004). As for the PGC-1alpha gene, there was no difference of the genotypic and allelic frequencies between the two groups (P>0.05). In NAFLD patients, the plasma adiponectin concentrations were lower in the PPAR-gamma CT/TT genotypes compared with those in the CC genotype group (3.0+/-0.6 vs. 4.3+/-0.9, P=0.02). Multivariate logistic regression analysis showed that CT/TT genotypes of PPAR-gamma, TG, waist hip ratio, hypoadiponectinaemia and homoeostasis model assessment (HOMA)-IR were the risk factors for NAFLD.


CONCLUSIONS
SNPs in the PPAR-gamma, but not PGC-1alpha, gene are associated with NAFLD susceptibility possibly through the adiponectin pathway.
Hui
Yang
Y
Department of Gastroenterology and Hepatology, First Municipal's People Hospital of Guangzhou, Guangzhou Medical College, Guangzhou, China.
Yu-Yuan
Li
L
Yu-Qiang
Nie
N
Wei-Hong
Sha
S
Yan-Lei
Du
D
Xiao-Bo
Lai
L
Yong-Jian
Zhou
Z
D052242:Adiponectin / Q000097:blood*; D044466:Asian People; D001837:Body Weights and Measures; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D052242:Adiponectin; D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors