Abstract 1896: Chromosome 9p21 Polymorphism Interacts With Waist-to-Hip Ratio in Carotid Plaque
Background: A gene-environment interaction has been suggested between a chromosome 9p21 polymorphism, which confers a major risk for cardiovascular disease, and waist-to-hip ratio (WHR). We further characterized this interaction for carotid atherosclerosis in the larger population-based Asklepios study.
Methods and Results: We genotyped the rs1333049 polymorphism on chromosome 9p21 in 2,481 healthy individuals aged 35 to 55 years, in which atherosclerotic plaque and intima-media thickness (IMT) were measured in both carotid arteries by a single investigator. We found that the rs1333049 C risk-allele was significantly associated with plaque in carotid arteries in both age- and gender-adjusted and multivariable-adjusted models (Table⇓). No association was seen with IMT. Interestingly, rs1333049 interacted significantly with WHR (P-values of interaction for plaque in left, right and bilateral carotid arteries, respectively, corrected for age and gender: P=0.029; 0.051 and 0.004; multivariable adjusted: P= 0.035; 0.020 and 0.002). Stratification of the cohort according to a WHR equal to or above and below the mean (0.78 for women and 0.92 for men), showed that the risk effect of rs1333049 was confined to abdominal obese individuals only (Table⇓). Stratification by WHO abdominal obesity criteria yielded similar results. No significant interaction was seen for IMT.
Conclusion: We confirm the interaction between the rs1333049 polymorphism on 9p21 and WHR and demonstrate that the rs1333049 risk-allele increases carotid plaque in abdominal obese individuals only. With the prevalence of obesity increasing rapidly, this interaction is of importance for cardiovascular disease.