title: Genetic variants in peroxisome proliferator-activated receptor-γ and retinoid X receptor-α gene and type 2 diabetes risk: a case-control study of a Chinese Han population.
abstract: BACKGROUND
  The serum levels of adiponectin are paradoxically decreased in obesity and may play important roles in the development of type 2 diabetes mellitus (T2DM). Potentially functional polymorphisms in the peroxisome proliferator-activated receptor-γ (PPAR-γ) and retinoid X receptor-α (RXR-α) genes may alter T2DM risks by increasing the human adiponectin promoter activity in cells. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in PPAR-γ and RXR-α were associated with risk of T2DM. To test this hypothesis, three potentially functional SNPs of PPAR-γ and four of RXR-α with a minor allele frequency of ≥ 0.05 in the Chinese Han population were identified from the National Center for Biotechnology Information dbSNPs database to evaluate their association with T2DM.
  
  
  METHODS
  Polymerase chain reaction-restriction fragment length polymorphism was performed to test the genotypes in T2DM patients (n = 540) and normal controls (n = 604).
  
  
  RESULTS
  The variant genotypes rs2920502CC, rs3856806CT, rs3856806CT/TT, and rs4240711AG/GG were associated with T2DM. Furthermore, the prevalences of haplotype GTC and CTG in PPAR-γ and GTAC in RXR-α were less frequent in cases (17.1%, 2.6%, and 2.4%, respectively) than in controls (22.3%, 3.8%, and 6.6%, respectively), whereas GTGT in RXR-α was more frequent in cases (6.9%) than in controls (4.4%) (P < 0.05 for both two-sided χ(2) test and thousand times permutation tests). Patients with genotype CT/TT of rs3856806 and genotype AG/GG of rs4240711 had higher levels of serum adiponectin than those with the genotype CC and genotype AA (P = 0.026 and 0.021, respectively). Model X2 X5 X6 X7 (rs3856806, rs3132291, rs4240711, and rs4842194) was the best model with the highest test balanced accuracy (0.5764) (cross-validation consistency = 10/10) in the multifactor dimensionality reduction method.
  
  
  CONCLUSIONS
  The PPAR-γ and RXR-α gene variants associated with the development of T2DM in this study must be investigated in a larger population to reveal any potential effects on metabolism.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Ye
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.forename: Jinluo
authors.initials: J
authors.lastname: Cheng
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ma
authors.forename: Wencong
authors.initials: W
authors.lastname: Du
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D047490:Retinoid X Receptor alpha / Q000235:genetics*
chemical_list: D052242:Adiponectin; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha