Abstract 21094: Evaluation of Inflammatory and Thrombotic Candidate Genes with Incident Diabetes in Women
Background: Inflammation and thrombosis are linked with the development of type 2 diabetes. The aim of the present study was to evaluate for potential associations of 77 previously characterized gene variants from 52 genes, chosen for involvement in inflammatory and thrombotic pathways with incident diabetes.
Methods: We analyzed data from 22,372 Caucasian women who participated in a prospective cohort study, the Women's Genome Health Study, and were free of diabetes at baseline (hemoglobin A1c <6.5%). Incident diabetes during the entire follow-up according to the different genotypes was assessed by Cox proportional hazard models.
Results: During a median follow-up of 12.3 years, 1206 of 22,372 women developed incident diabetes. Only two of 70 polymorphisms with a minor allele frequency ≥2% were modestly associated with incident diabetes. The hazard ratios (HRs) (95% confidence interval (CI)) for ADRB2 rs1042713 and AGT rs699 were 1.09 (1.01-1.19) and 1.08 (0.99-1.17), respectively. After adjustment for body mass index in WHO categories, the relationships persisted with hazard ratios (95% CI) of 1.09 (1.00-1.18) and 1.09 (1.00-1.18) respectively. Only AGT rs699 remained modestly associated with incident diabetes in fully adjusted models that adjusted additionally for age, hypertension, smoking, hormone use, exercise, alcohol use, total cholesterol and high density lipoprotein levels. After adjustment for multiple testing, using the false discovery rate, none of these associations remained significant.
Conclusion: These prospective data suggest that ADRB2 and AGT gene polymorphisms may have a potential role in the development of incident diabetes. Although both gene variants failed to meet criteria for association after adjustment for multiple testing, our findings provide validation for previous cross-sectional studies that relate rs1042713 to metabolic syndrome and obesity and rs699 to glycated hemoglobin.
- © 2010 by American Heart Association, Inc.