去甲肾上腺素转运体基因启动子多态性及单倍体型与高血压病血瘀证的相关性研究

Relationship between Gene Polymorphism and Haplotype of SLC6A2 Promoter and Blood-stasis Pattern in Patients with Essential Hypertension

目的探讨去甲肾上腺素转运体(SLC6A2)基因启动子2、3多态性及单倍体型与高血压病血瘀证的关系。方法收集高血压病血瘀证患者532例,高血压病非血瘀证患者298例,血压正常对照者512名,采外周静脉血提取DNA,采用PCR-RFLP法检测SLC6A2基因启动子2、3多态性,SHEsis软件构建单倍体数量。结果χ2分割显示高血压病血瘀证组的启动子2-GG频率低于非血瘀证组和对照组(P=0.001),重度血瘀组的启动子3-GG/GA频率高于其余组别(P<0.001)。Logistic回归分析显示,调整混杂因素后,启动子2-GC/CC型患高血压病血瘀证的相对危险度(OR)为1.535(95%CI:1.094～2.155,P=0.013);启动子3-AG/GG型患高血压病重度血瘀证的OR为1.925(95%CI:1.199～3.091,P=0.007);G-C单倍体(启动子3-2)患高血压病血瘀证的OR为2.127(95%CI:1.202～3.765,P=0.010),预测强度最大。结论携带SLC6A2基因启动子3-AG/GG型可能是高血压病重度血瘀证易患基因,启动子2-GC/GC、G-C单倍体可能是血瘀证易患因素之一。

Objective To explore the relationship between the genetic variants of the norepinephrine transporter gene solute carrier family 6 member 2 （SLC6A2） and blood stasis pattern （BSP） in patients with essential hypertension （EH）. Methods DNA was extracted from the peripheral blood of 830 EH patients （532 were typed as BSP and 298 as non-BSS） and 512 persons with normal blood pressure （for control）, to detect the polymorphisms of SLC6A2 promoter-3 and 2 by PCR-RFLP, and estimate the haplotype frequency adopting SHEsis program. Results χ2 partition showed that frequency of promoter-2-GG genotype in EH patients of BSP was lower than that in the EH patients of non-BSP and the normal control （P=0.001）; while that of promoter-3-GG/GA in the EH patients with severe BSP was the highest （P0.001）. Logistic regression analysis showed that after the miscellaneous factors being rectified, with the reference category of EH-non-BSP, the relative odds ratio （OR） of promoter-2-GC/CC genotype for EH-BSP was 1.535 （95%CI： 1.094-2.155, P=0.013）; that of promoter-3-AG/GG genotype for EH with severe BSP was 1.925 （95%CI： 1.199-3.091, P=0.007）; while OR of G-C haplotype （promoter-3-promoter-2） for EH-BSP was 2.127 （95%CI： 1.202-3.765, P=0.010）, showing the strongest intensity.Conclusion SLC6A2 promoter-3-GA/GG genotype may be a susceptibility gene for patients of EH with severe BSP; promoter2-GC/CC and G-C haplotype might be the susceptible factors to EH-BSP.