Common genetic variants in peroxisome proliferator-activated receptor-γ (PPARG) and type 2 diabetes risk among women's health initiative postmenopausal women

Kei Hang K. Chan, Tianhua Niu, Yunsheng Ma, Nai Chieh Y. You, Yiqing Song, Eric M. Sobel, Yi Hsiang Hsu, Raji Balasubramanian, Yongxia Qiao, Lesley Tinker, Simin Liu

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Abstract

Context: 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). Research Design and 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 ORs0.68-0.78, 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.

Original languageEnglish (US)
Pages (from-to)E600-E604
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number3
DOIs
StatePublished - Mar 1 2013

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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