Common genetic variants in peroxisome proliferator-activated receptor-γ (PPARG) and type 2 diabetes risk among Women's Health Initiative postmenopausal women.
J Clin Endocrinol Metab
; 98(3): E600-4, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23386649
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 ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pós-Menopausa
/
PPAR gama
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos