Variants in candidate genes and their interactions with smoking on the risk of acute coronary syndrome

Introduction. Multiple genetic and environmental factors interact with the development of acute coronary syndrome. Smoking is one of the environmental factors that might alter the metabolic pathways shared by genes associated with this condition. Objective. To investigate the association of acute coronary syndrome with genetic variants related to inflammation, lipid metabolism, and platelet aggregation among subjects from the northeastern region of Colombia. The effects of interactions between polymorphisms and smoking were also evaluated. Materials and methods. We analyzed data from 330 acute coronary syndrome cases and 430 controls. Associations between 20 polymorphisms and acute coronary syndrome were evaluated using logistic regression, adjusting for confounders. Gene and smoking interaction terms were calculated, and variants were analyzed separately in smokers and non-smokers for their association with acute coronary syndrome. Results. Two variants were associated with acute coronary syndrome, rs10455872 in the LPA gene (OR = 2.69; 95% CI: 1.61–4.49) and rs429358 in the APOE gene (OR = 1.93; 95% CI: 1.30–2.87). We identified smoking interactions with the variants rs6511720 in the LDLR gene (p = 0.04) and rs2227631 in the SERPINE1 gene (p = 0.02), with significant effects in non-smokers (rs6511720: OR = 0.40; 95% CI: 0.19–0.88; and rs2227631: OR = 0.69; 95% CI: 0.48–1.00), but not in smokers (rs6511720: OR = 1.28; 95% CI: 0.66–2.46; and rs2227631: OR = 1.30; 95% CI: 0.91–1.87). Conclusions. Variants in the candidate genes LPA and APOE are associated with an increased risk of acute coronary syndrome in a population from northeastern Colombia. The effects of rs6511720 in LDLR and rs2227631 in SERPINE1 differ according to smoking habits and are significant in non-smokers. These results are helpful for early risk screening of acute coronary syndrome, mainly in individuals without defined conventional risk factors.