Abstract 17540: the CC Variant of Locus 9p21 Increases Coronary Disease Risk with High Values of Hs-CRP

Recent genomic wide association studies have identified several loci associated with coronary artery disease (CAD) risk. Among them, SNP rs 1333049 in the locus 9p21 (variant CC) has demonstrated a solid association with CAD which has been replicated in several populations, namely ours. High sensibility C-reactive protein (hs-CRP) has also been associated with inflammatory activity and atherosclerosis. An eventual interaction among these two atherosclerotic markers is unknown. Aim: To explore the interaction between this homozygous genetic variant (CC) and hs-CRP plasmatic levels in the emergence of CAD. Methods: Case-control study with 1561 participants, 695 consecutive coronary patients (mean age 53.9±8.9 years, 78.8% male) and 838 controls without apparent CAD (mean age 52.0±11.4 years, 71% male) selected in order not to present significant differences in sex and age. The G/C variants were studied blindly using a combined technique of PCR and TaqMan. Hardy-Weinberg distribution was analyzed. The CAD risk was investigated by univariate analysis and the OR and 95% confidence intervals were calculated. hs-CRP values were distributed by quartiles and the highest one, considered as the risk, was evaluated. To determine the interaction between CC genotype and elevated hs-CRP values we used a 4x2 table approach, as well as synergy measurements in additive (SI) and multiplicative (SIM) models. Finally, the risk excess (RERI) and the attributable proportion (AP) due to the interaction were calculated. Results: The CC variant was significantly associated with CAD risk in the whole population (OR=1.32; p=0.011). The presence of this genetic variant with normal hs-CRP values presented a smaller risk (OR=1.28) when compared to the association with the elevated hs-CRP values in the highest quartile (OR=1.7; p=0.007; SI=1.63; SIM=1.15; RERI=0.27). Conclusion: The present study demonstrates that the CC variant of the 9p21 locus globally increases the risk of CAD. This risk can be further increased in the presence of elevated hs-CRP values, as shown by the addictive and multiplicative interaction. This concept allows us to foresee the possibility of genetic risk factors management through the control of associated conditions, whenever possible.