title: Association and interaction of PPARα, δ, and γ gene polymorphisms with low-density lipoprotein-cholesterol in a Chinese Han population.
abstract: OBJECTIVE
  Elevated low-density lipoprotein-cholesterol (LDL-C) is regarded as one of major risks of cardiovascular diseases and atherosclerotic events. It has been previously reported that peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of lipid metabolism. In this study, we aimed to investigate the influence of PPARα/δ/γ gene polymorphisms on LDL-C level. Eight hundred twenty unrelated participants were recruited. Ten single-nucleotide polymorphisms (SNPs) were genotyped to analyze the gene-gene interactions among these polymorphisms using the generalized multifactor dimensionality reduction (GMDR) method.
  
  
  RESULTS
  The results of single-locus analyses indicated that the genotypes with minor allele variants at the rs1800206, rs9794, rs1805192, rs709158, and rs3856806 loci are associated with higher LDL-C levels (p<0.05) after adjusting for covariates. In contrast, individuals that were homozygous for the major allele (CC) of rs10865710 had significantly higher LDL-C than those with either one or more minor type alleles (CG+GG, mean difference: -0.21 mM; 95% confidence interval [CI]: -0.37 to -0.04 mM; p=0.013). Significant gene-gene interactions among PPAR gene polymorphisms on LDL-C were identified by a generalized multifactor dimensionality reduction (GMDR) approach in 2- to 8-locus models (p<0.05).
  
  
  CONCLUSIONS
  Our results provide evidence that multiple PPARα/δ/γ gene polymorphisms are individually associated with increased LDL-C, and that interactions, among these alleles result in additional increased risk suggesting that PPAR genes may contribute substantially to the risk of cardiovascular diseases and atherosclerosis.
authors.affiliation: 1 Department of Epidemiology, School of Public Health, Medical College of Soochow University , Suzhou, China .
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: 1 Department of Epidemiology, School of Public Health, Medical College of Soochow University , Suzhou, China .
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: 2 Center for Disease Control of Jiangsu Province , Nanjing, China .
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: 3 Center for Disease Control of Changshu , Suzhou, China .
authors.forename: Zheng-Yuan
authors.initials: ZY
authors.lastname: Zhou
authors.affiliation: 1 Department of Epidemiology, School of Public Health, Medical College of Soochow University , Suzhou, China .
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Guo
mesh_terms: D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D002681:China; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D047494:PPAR delta / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D047492:Peroxisome Proliferator-Activated Receptors / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008078:Cholesterol, LDL; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors