Common genetic variants in peroxisome proliferator-activated receptor-gamma (PPARG) and type 2 diabetes risk among Women's Health Initiative postmenopausal women
Department of Medicine, Division of Preventive and Behavioral Medicine
Adipogenesis; African Americans; Aged; Asian Americans; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; European Continental Ancestry Group; Female; Haplotypes; Hispanic Americans; Humans; Logistic Models; Middle Aged; Multivariate Analysis; PPAR gamma; Polymorphism, Single Nucleotide; Postmenopause; Risk Factors; United States
Cellular and Molecular Physiology | Endocrinology | Nutritional and Metabolic Diseases | Women's Health
CONTEXT: Peroxisome proliferator-activated receptor-gamma (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 ORs 0.68-0.78, 95% CIs 0.52-0.91 to 0.60-1.00, P
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.
Chan, Kei Hang K.; Niu, Tianhua; Ma, Yunsheng; You, Nai-chieh Y; Song, Yiqing; Sobel, Eric M.; Hsu, Yi-Hsiang; Balasubramanian, Raji; Qiao, Yongxia; Tinker, Lesley F.; and Liu, Simin, "Common genetic variants in peroxisome proliferator-activated receptor-gamma (PPARG) and type 2 diabetes risk among Women's Health Initiative postmenopausal women" (2013). Preventive and Behavioral Medicine Publications and Presentations. 268.