Department of General Medicine, Longhua District Central Hospital, Shenzhen, 518110, China.
Department of Cardiovascular Medicine, Mudanjiang Second People's Hospital, Mudanjiang, 15700, China.
J Thromb Thrombolysis. 2019 Jan;47(1):67-72. doi: 10.1007/s11239-018-1755-6.
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.
为了研究组织因子途径抑制剂-2（TFPI-2）基因多态性中单核苷酸多态性（SNP）与其他基因-环境相互作用与冠状动脉粥样硬化风险的关系。采用广义多因素降维分析（GMDR）筛选 4 个 SNP、吸烟和饮酒之间的最佳相互作用组合。采用 logistic 回归分析 TFPI-2 基因内 4 个 SNP 与冠状动脉粥样硬化风险的关系。TFPI-2 基因内 rs34489123 的 A 等位基因携带者的冠状动脉粥样硬化风险明显高于 GG 基因型（GA+AA 与 GG），调整后的比值比（95%CI）=1.70（1.20-2.31），TFPI-2 基因内 rs4264 的 G 等位基因携带者的冠状动脉粥样硬化风险也高于 AA 基因型（AG+GG 与 AA），调整后的比值比（95%CI）=1.62（1.21-2.11）。GMDR 模型显示，调整协变量后，rs34489123 与吸烟的基因-环境相互作用最佳模型得分为 10 分（交叉验证一致性）和 0.0010（符号检验）。SNP rs34489123 和 rs59805398 之间存在高度连锁不平衡（D'值大于 0.8）。与对照个体相比，AG 单倍型似乎与冠状动脉粥样硬化风险增加显著相关，比值比（95%CI）=1.73（1.22-2.32）。我们发现 TFPI-2 基因内 rs34489123 的 A 等位基因和 rs4264 的 G 等位基因、rs34489123 与吸烟的相互作用以及 AG 单倍型均与冠状动脉粥样硬化风险增加相关。
