Abstract 1805: Chromosome 9p21.3 Genetic Variation is Associated with Angiographic CAD but not with CAD Disease Burden
Genetic variation at the 9p21.3 locus rs2383206 is associated with coronary heart disease (CHD) phenotypes. In a comparison of patients with and without angiographically confirmed CHD, the G allele of rs2383206 was present more frequently in diseased vs controls (normal angiograms). However, the pathophysiologic impact, whether it affects initiation, severity, or triggers an event, of the 9p21.3 locus remains unknown. We sought to determine whether 9p21.3 variation affects disease severity (promotion) by assessing its association with CAD burden.
Methods: Genotyping for rs2383206 using 5′exonuclease chemistry (Taqman) was performed on 1759 subjects. Subjects were grouped as homozygous wild-type (low risk), heterozygous (intermediate risk) or homozygous risk-associated genotype (high risk). Disease burden was assessed by 1, 2, or 3 vessels; ≥70% stenosis and the validated Duke CAD Index (DCI). Comparison used a chi-square test (single vs multivessel disease) and analysis of variance (ANOVA) for the DCI comparison.
Results: Average age 51.1± 7.4 years, 64.0% male. Frequency of the CAD risk allele did not differ among groups with 1, 2, or 3 vessel disease. There was no difference among groups with respect to the DCI. After adjustment for standard cardiac risk factors, the rs2383206 genotype was associated with CAD compared to controls (OR (CI)=1.73(1.26–1.85), p=0.001).
Conclusion: The rs2383206 polymorphism was not associated with CAD disease burden. Findings suggest the rs2383206 polymorphism, although associated with disease onset is not likely involved in its progression. These findings will aid in refining the application of 9p21.3 for risk assessment and developing novel preventive and therapeutic strategies.