Abstract 13646: Genetic Variants, Glycemic Control and Risk of Coronary Heart Disease in Type 2 Diabetes
Type 2 diabetes has been associated with a 2-4 fold increased risk of coronary heart disease (CHD). Few studies have investigated the genetic determinations of CHD risk among diabetic patients. We previously confirmed 5 CHD loci (CDKN2A/2B, PHACTR1, CELSR2-PSRC1-SORT1, HNF1A, and PCSK9) indentified in the general population through genome-wide association studies (GWAS; before 2010) as being significantly associated with CHD risk among patients with type 2 diabetes. In the present study, we extended the study to 19 recently identified CHD loci from GWAS in the general population (after 2010) and evaluated the interaction between the CHD associated genetic variants and glycemic control estimated by HbA1c levels, in 982 men (317 CHD cases and 665 controls) and 1259 women (279 CHD cases and 980 controls) with type 2 diabetes from the Health Professionals Follow-up Study and the Nurses' Health Study. Among the newly identified loci, the SNP rs974819 in PDGFD locus showed a nominally significant association with CHD risk in men and women combined (OR [95% CI]: 1.17 [1.00-1.36], P=0.047), with consistent directions. In addition, we observed significant interactions between 2 SNPs, rs3825807 in ADAMTS7 and rs1746048 in CXCL12, and HbA1c levels on CHD risk (P for interaction =0.003 and 0.01, respectively). In participants with a higher HbA1c level (≥median), the ORs for CHD risk were 1.28 (1.01-1.63) and 0.81 (0.60-1.11); whereas in participants with a lower HbA1c level (<median) the ORs were 0.77 (0.60-0.99) and 1.51 (1.04-2.20), for each risk allele of SNPs rs3825807 and rs1746048, respectively. Our results suggest that glycemic control may modify the genetic effects on CHD risk in type 2 diabetes.
- © 2011 by American Heart Association, Inc.