Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the Han of China

Aims: To investigate the association of CYP1A1 genotype and additional gene-smoking interaction with coronary artery disease (CAD) risk based on a Chinese case-control study. Methods: A total of 1862 participants (1134 men, 728 women) were selected, including 620 CAD patients and 1242 normal controls. Logistic regression was performed to investigate association of CYP1A1 genotype, gene-gene, and gene-smoking interaction with CAD. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best gene-gene and gene-smoking interaction combination, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess if each selected interaction was calculated. Results: The carriers of homozygous mutant of rs4886605 polymorphism and heterozygous of rs4646903 are associated with increased CAD risk than those with wild-type homozygotes; OR (95% CI) was 1.98 (1.53-2.61) and 1.58 (1.24-1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism is associated with decreased CAD risk than those with wild-type homozygotes, OR (95% CI) = 0.75 (0.60-0.93). GMDR model indicated a potential gene-gene interaction between rs4886605 and rs4646903 and a potential gene-smoking interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT and rs4646903-TC or CC genotype have the highest CAD risk, compared to participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72 (2.03-3.61). In addition, we also found that smokers with rs4886605-CT or TT genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC genotype; OR (95% CI) was 3.07 (2.23-3.96). Conclusions: rs4886605 and rs4646903 are associated with increased CAD risk, but rs1048943 is associated with decreased CAD risk; we also found gene-gene interaction between rs4886605 and rs4646903 and gene-environment interaction between rs4886605 and smoking.