摘要
目的:探讨缓激肽β2受体基因启动子区-58T/C、内皮型一氧化氮合酶G894T多态性在中国汉族原发性高血压患者中的分布及其与血管紧张素转换酶抑制剂降压疗效之间的关系。方法:①选择2000-09/2001-09全国多中心临床试验入组的1～2级无血缘关系的原发性高血压患者365例,男216例,女145例。均签署知情同意书。经安慰剂治疗2周后,血压符合入选标准者分别给予血管紧张素转换酶抑制剂咪达普利5～10mg/d或贝那普利10～20mg/d,治疗6周。②用酚-氯仿法提取基因组DNA,采用聚合酶链式反应分别结合单链构象多态性、限制性内切酶片段长度多态性方法检测缓激肽β2受体、内皮型一氧化氮合酶基因型,分析不同基因型与血管紧张素转换酶抑制剂降压疗效的关系。③不同基因型组间计量资料的比较采用方差分析,计数资料的比较采用χ2检验,遗传平衡检验采用Hardy-Weinberg平衡定律。结果:进行缓激肽β2受体基因和内皮型一氧化氮合酶基因分析成功361和365例进入结果分析。①中国汉族365例原发性高血压患者中TT,TC,CC基因型频率分别为12.00%,61.50%,26.50%,等位基因C,T的频率分别为0.59和0.41。内皮型一氧化氮合酶基因GG,GT,TT基因型频率分别为64.65%,29.53%,5.82%,等位基因G,T的频率分别为0.79和0.21。经检验基因型分布符合Hardy-Weinberg平衡,达到了遗传平衡,具有群体代表性。②缓激肽β2受体基因TT,TC和CC基因型患者治疗前血压基础值差异不明显(P>0.05),治疗后TT,TC基因型患者收缩压和舒张压下降幅度均明显高于CC基因型(P<0.05～0.01)。内皮型一氧化氮合酶基因GG,GT,TT基因型患者收缩压与舒张压下降值差异不明显。③在男性患者中,缓激肽β2受体基因(TC+TT)+内皮型一氧化氮合酶基因GG及缓激肽β2受体基因CC+内皮型一氧化氮合酶基因(GT+TT)患者收缩压下降幅度明显低于缓激肽β2受体基因(TC+TT)+内皮型一氧化氮合酶基因(GT+TT)(P<0.05)。结论:①携带T等位基因的中国汉族原发性高血压患者血管紧张素转换酶抑制剂降压效果好。②内皮型一氧化氮合酶单一基因多态性对降压疗效影响很小,也可能与降压疗效无关。③内皮型一氧化氮合酶基因与缓激肽β2受体基因对收缩压的下降幅度有交互作用,且有性别差异。
AIM： To investigate the distribution of -58T/C polymorphism of the bradykinin β2 receptor gene （BDKRB2）and the G894T polymorphism of the endothelial nitric oxide synthase （eNOS） in Han Chinese essential hypertensive patients and the relationship between genotype and antihypertensive response to angiotensin converting enzyme inhibitor （ACE1）.
METHODS： ①365 patients （216 males and 145 females） with essential hypertension were selected from many national clinical test center without 1-2 grade blood relationship between September 2000 and September 2001. They all agreed to take part in the experiment. After 2 weeks of being treated with placebo, the patients who accorded with the inclusion criteria were administered with imidapril 5 to 10 mg per day or benazepril 10 to 20 mg per day for six weeks, respectively. ②Genotype of BDKRB2 and eNOS gene were determined by the polymerase chain reaction （PCR） combined with single-strand conformation pelymorphism （SSCP） and restriction fragment length polymorphism （RFLP） respectively. Relation between different genotype and decompression effect of ACEI was analyzed. ③Measurement data at different genotype were compared with analysis of variance. Enumeration data were compared with x^2 test. Genetic equilibrium test was performed with Hardy-Weinberg equilibrium law.
RESULTS： BDKRB2 gene with 361 successful cases and eNOS gene with 365 successful cases were involved in the result analysis. ①Among the 365 Han Chinese essential hypertension patients, the genotype frequencies of BDKRB2 gene were 12.00% for TY,61.50% for TC ,and 26.50% for CC, the allele frequencies for T and C were 0.41 and 0.59. The genotype frequencies of eNOS gene were 64.65% for GG,29.53% for GT and 5.82% for TT , the allele frequencies for G and T were 0.79 and 0.21. After examination, the distribution of genotype accorded with Hardy-Weinberg equilibrium, reached genetic equilibrium, and had representativeness. ②Difference of blood pressure basic value of TT,TC and CC genotype of BDKRB2 gene was insignificant before treatment （P 〉 0.05）, and after treatment the reduction of systolic pressure and diastolic pressure in patients carrying TT, TC genotype was higher than those carrying CC genotype （P 〈 0.05-0.01 ）. The reduction of systolic pressure and diastolic pressure in patients carrying GG,GT and TT genotype for eNOS had insignificant difference. ③Among the male patients, the reduction of systolic pressure of BDKRB2 gene （TC ＋ TT）＋ eNOS GG and BDKRB2 gene CC ＋ eNOS （GT＋TT）was lower significantly than those of BDKRB2 gene （TC ＋ TT）＋ eNOS gene （GT＋TT）（P 〈 0.05）.
CONCLUSION： ①ACE1 has better decompression effect in Han Chinese essential hypertension patients carrying the T allele for BDKRB2 gene. ②Simple gene polymorphism of eNOS has small effects on decompression, which is possibly irrelated to the efficacy of decompression. ③BDKRB2 and eNOS gene may exert interaction in the reduction of systolic pressure, and have sex difference.
出处
《中国临床康复》
CSCD
北大核心
2006年第4期19-22,共4页
Chinese Journal of Clinical Rehabilitation
基金
杨森科学委员会(JRCC)基金项目(2002-2004)~~
