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.
DOI of Published Version
J Clin Endocrinol Metab. 2013 Mar;98(3):E600-4. doi: 10.1210/jc.2012-3644. Link to article on publisher's site
The Journal of clinical endocrinology and metabolism
Chan K, Niu T, Ma Y, You N, Song Y, Sobel EM, Hsu Y, Balasubramanian R, Qiao Y, Tinker LF, Liu S. (2013). Common genetic variants in peroxisome proliferator-activated receptor-gamma (PPARG) and type 2 diabetes risk among Women's Health Initiative postmenopausal women. Preventive and Behavioral Medicine Publications. https://doi.org/10.1210/jc.2012-3644. Retrieved from https://escholarship.umassmed.edu/prevbeh_pp/268