Interaction between tissue factor pathway inhibitor-2 gene polymorphisms and environmental factors associated with coronary atherosclerosis in a Chinese Han

To investigate the association of single nucleotide polymorphisms (SNPs) within tissue factor pathway inhibitor-2 (TFPI-2) gene polymorphisms and additional gene-environment interaction with coronary atherosclerosis risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs, smoking and alcohol drinking. Logistic regression was performed to investigate association between 4 SNPs within TFPI-2 gene and coronary atherosclerosis risk. Coronary atherosclerosis risk was significantly higher in carriers with the A allele of rs34489123 within TFPI-2 gene than those with GG genotype (GA+AA versus GG), adjusted OR (95% CI)=1.70 (1.20-2.31), and was also higher in carriers with the G allele of rs4264 within TFPI-2 gene than those with AA genotype (AG+GG versus AA), adjusted OR (95% CI)=1.62 (1.21-2.11). GMDR model shown the best models for gene-environment interaction were rs34489123 and smoking after adjusting the covariates, which scored 10 out of 10 for cross-validation consistency and 0.0010 for the sign test. Heavy LD was found for SNPs rs34489123 and rs59805398 (D' value was more than 0.8). Compared to control individuals, the AG haplotypes appeared to be significantly associated with increased coronary atherosclerosis risk, OR (95% CI)=1.73 (1.22-2.32). We found that the A allele of rs34489123 and the G allele of rs4264 within TFPI-2 gene, interaction between rs34489123 and smoking and AG haplotypes were all associated with increased coronary atherosclerosis risk.