一氧化氮合酶基因多态性与常用降压药疗效的关联研究

目的:探讨一氧化氮合酶（NOS3)基因的遗传变异对常用降压药物疗效的影响。方法: 收集服用复方利血平、降压片和珍菊降压片的原发性高血压患者一般情况和临床生化指标资料。采用聚合酶链反应(PCR)和限制性片断长度多态性(RFLP)检测NOS3基因上所选3个位点多态性，运用一般线性模型统计方法分析服用不同降压药物后不同基因型间血压水平的变化。结果: 在服用降压片的原发性高血压患者中，rs1808593位点与舒张压的水平呈线性相关，TT基因型的患者舒张压水平高于TG、GG基因型患者，校正协变量后，差异仍有统计学意义（P=0.035）。进一步分层分析显示，在服用降压片的男性原发性高血压患者中，rs1808593位点与舒张压的水平呈线性相关，TT基因型的患者舒张压高于TG、GG基因型患者的舒张压（P=0.046）；同时在服用降压片的≥55岁原发性高血压患者中，rs1808593位点TT基因型的患者舒张压亦高于TG、GG基因型病人的舒张压（P=0.008）。结论:NOS3基因rs1808593突变可能与降压片的降压效果相关。

Association study of NOS3 genetic polymorphism and the efficacy of anti-hypertensive drug treatment on patient with essential hypertension

AIM: To evaluate the effect of NOS3 gene polymorphism on anti-hypertensive drug treatment for patient with essential hypertension (EH). METHODS: General information and Clinical biochemical indicators of EH patients taking compound reserpine, hypertension pill and Zhenju hypertension pill were collected. RELP-PCR was used to test the polymorphism of NOS3 gene (rs4496877, rs1808593 and rs3918186).A quantitative trait analysis was performed to evaluate the relation between NOS3 genetic variation and blood pressure taking different anti-hypertensive drugs. RESULTS: Quantitative trait analysis showed significant differences in diastolic blood pressure (DBP) among the genotypes (TT,TG and GG) of rs1808593 in patients taking the hypertension pill after adjusting covariants (P=0.035). Stratification analysis indicated that DBP of male patients taking the hypertension pill significantly decreased with the variation (T＞G) of rs1808593 (P=0.046). For patients (age≥55) taking the hypertension pill, DBP of genotype TT was significantly higher than genotypes TG and GG of rs1808593(P=0.008). CONCLUSION: NOS3 gene rs1808593 mutation might relate to the anti-hypertensive effect of the hypertension pill.