title: Common genetic variants in peroxisome proliferator-activated receptor-γ (PPARG) and type 2 diabetes risk among Women's Health Initiative postmenopausal women.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor-γ (PPARG) plays a pivotal role in adipogenesis and glucose homeostasis.
  
  
  OBJECTIVE
  We investigated whether PPARG gene variants were associated with type 2 diabetes (T2D) risk in the multiethnic Women's Health Initiative (WHI).
  
  
  METHODS
  We assessed PPARG single-nucleotide polymorphisms (SNPs) in a case-control study nested in the prospective WHI observational study (WHI-OS) (1543 T2D cases and 2170 matched controls). After identifying 24 tagSNPs, we used multivariable logistic regression models and haplotype-based analyses to estimate these tagSNP-T2D associations. Single-SNP analyses were also conducted in another study of 5642 African American and Hispanic American women in the WHI SNP Health Association Resource (WHI-SHARe).
  
  
  RESULTS
  We found a borderline significant association between the Pro12Ala (rs1801282) variant and T2D risk in WHI-OS [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.31-0.83, P = .01, combined group, additive model; P = .04, Hispanic American] and WHI-SHARe (OR 0.25, 95% CI 0.08-0.77, P = .02, Hispanic American) participants. In promoter region, rs6809631, rs9817428, rs10510411, rs12629293, and rs12636454 were also associated with T2D risk (range ORs 0.68-0.78, 95% CIs 0.52-0.91 to 0.60-1.00, P ≤ .05) in WHI-OS, in which rs9817428 was replicated in then WHI-SHARe Hispanic American group (P = .04).
  
  
  CONCLUSIONS
  The association between PPARG Pro12Ala SNP and increased T2D susceptibility was confirmed, with Pro12 as risk allele. Additional significant loci included 5 PPARG promoter variants.
authors: Department of Epidemiology, Center for Metabolic Disease Prevention, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
authors: Kei Hang K
authors: KH
authors: Chan
authors: Tianhua
authors: T
authors: Niu
authors: Yunsheng
authors: Y
authors: Ma
authors: Nai-chieh Y
authors: NC
authors: You
authors: Yiqing
authors: Y
authors: Song
authors: Eric M
authors: EM
authors: Sobel
authors: Yi-Hsiang
authors: YH
authors: Hsu
authors: Raji
authors: R
authors: Balasubramanian
authors: Yongxia
authors: Y
authors: Qiao
authors: Lesley
authors: L
authors: Tinker
authors: Simin
authors: S
authors: Liu
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D000368:Aged; D001213:Asian / Q000235:genetics / Q000706:statistics & numerical data; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D001786:Blood Glucose; D047495:PPAR gamma
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