ET-1 Lys198Asn和eNOS Glu298Asp基因多态性与原发性高血压及硝苯地平降压疗效的相关性  

The association of genetic polymorphisms of ET-1 Lys198Asn and eNOS Glu298Asp with essential hypertension and antihypertensive effect of nifedipine

作　　者：江承设[1] 李栋[1] 余运贤[1] 彭少杰 李建平[3] 黄爱群[1] 徐希平[1] 

机构地区：[1]中国科学技术大学生命科学学院,合肥230027 [2]上海市疾病控制中心,上海200083 [3]北京大学附属第一医院,北京100034

出　　处：《中国药理学通报》2003年第8期875-879,共5页Chinese Pharmacological Bulletin

摘　　要：目的　研究安徽省 1个高血压人群中内皮素 1 (ET 1 )基因位于第 5号外显子的第 1 98位密码子G/T多态性导致的赖氨酸 /天冬酰胺 (Lys1 98Asn)突变以及内源性一氧化氮合成酶 (eNOS)基因第 2 98位密码子的G/T多态性导致的谷氨酸 /天冬氨酸 (Glu2 98Asp)突变与原发性高血压及抗高血压药物硝苯地平降压疗效的相关性。方法　 1 1 0 8例初诊或已停药 2wk以上的原发性高血压病人 ,口服硝苯地平类药物 (拜新同 30mg·d- 1 ) 1 5d。分别按照收缩压及舒张压的降压效果 ,选取降压效果最好及最差的各 1 0 0例病人。这样 ,共 2 93例病人入选该研究。基因型测定采用PCR RFLP方法。分别按收缩压和舒张压 ,对两极端组病人基因多态性与基线血压及降压效果进行分析。结果　在两组极端组组成的总人群中 ,ET 1基因多态性中TT纯合子基因型受试者的基线舒张压〔DBP =(1 0 3 3± 1 6)mmHg〕(1kPa =7 5mmHg)高于带有G等位基因 (GG/GT)的受试者DBP =(99 4± 0 5)mmHg〕 (P =0 0 2 )。ET 1的Lys1 98Asn多态性和eNOS的Glu2 98Asp多态性与拜新同降压效果的关系 ,无论以收缩压还是以舒张压来分 ,均无显著相关性。结论　在该研究的高血压人群中ET 1的Lys1 98Asn多态性与基线舒张压相关。ET 1Lys1 98Asn多态性和eNOSGlu2 98Asp多态性?AIM To investigate the association of endothelin-1 gene(ET-1) Lys198Asn polymorphism and endothelial nitric oxide synthase gene (eNOS ) Glu298Asp polymorphism with baseline blood pressure value and antihypertensiv e effect of nifedipine in a Chinese hypertensive population. METHODS A total of 1108 essential hypertensive subjects were treated with nifedipine 30 mg·d -1 for 15 consecutive days. Based on their blood pressure respons e to nifedipine, a total of 293 subjects were regrouped into two categories: the y were either in the top 100 subjects whose systolic blood pressure (SBP) or dia stolic blood pressure (DBP) decreased the most in response to nifedipine or the bottom 100 subjects whose SBP or DBP showed the least response to nifedipine. Po lymerase chain reaction (PCR) followed by restriction enzyme digestion was used for genotyping the two single nucleotide polymorphisms (SNP). RESULTS The baseline DBP among subjects with GG genotype 〔DBP=(103 3±1 6) mm Hg〕 of the ET-1 Lys198Asn polymorphism was significantly higher than those wit h GT/TT genotypes〔DBP=(99 4±0 5) mmHg〕(P=0 02). Neither the ET-1 Ly s198Asn polymorphism nor the eNOS Glu298Asp polymorphism has a significant relat ionship with the antihypertensive effect of nifedipine. CONCLUSION In this study of hypertensive population, there is no significant association of the Lys198Asn polymorphism of ET-1 and the Glu298Asp polymorphism of eNOS wi th the antihypertensive effect of nifedipine. However, we found that ET-1 Lys19 8Asn polymorphism was significantly associated with baseline DBP.

关 键 词：内皮素-1 一氧化氮合成酶 多态性 硝苯地平 高血压 降压疗效 

分 类 号：R394.2[医药卫生—医学遗传学] R544.1[医药卫生—基础医学]