| 吕筠,李立明,詹思延,杨慧英,李晓晖,曹卫华,胡永华.苯那普利咳嗽不良反应候选基因研究[J].Chinese journal of Epidemiology,2003,24(6):498-502 |
| 苯那普利咳嗽不良反应候选基因研究 |
| Study on candidate genes of benazepril related cough in Chinese hypertensives |
| Received:October 10, 2002 |
| DOI： |
| KeyWord: 血管紧张素转换酶抑制剂 咳嗽 血管紧张素转换酶 缓激肽 受体 基因 |
| English Key Word: Angiotensin converting enzyme inhibitor Cough Angiotensin converting enzyme Bradykinin receptor Gene |
| FundProject:国家“九五”科技攻关课题资助项目(96-906-02-05) |
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| Abstract: |
| 目的探讨血管紧张素转换酶(ACE)基因I/D多态性和缓激肽β2受体(BDKRB2)基因C/T多态性与苯那普利相关的咳嗽不良反应间的关联。方法在对1831例高血压患者进行苯那普利3年上市后监测的基础上,嵌套病例对照研究。采用分层随机抽样方法,从与病例对应的年龄、性别和肾功能状态组内随机抽取对照。结果ACEI/D等位基因频率为I65.4%、D34.6%,BDKRB2C/T频率为T53.0%、C47.0%。基因型频率分别为II42.2%、ID46.4%、DD11.4%(ACE基因);以及CC21.6%、CT50.9%、TT27.6%(BDKRB2基因)。BDKRB2C/T与咳嗽间未发现有统计学意义的关联。肾功能失代偿的男性组中,ID或DD基因型发生咳嗽的OR值为4.805。肾功能正常或代偿的35～49岁女性组中DD基因型对应的OR值为5.128。其他亚组未发现差异有显著统计学意义。结论D等位基因对应较高的咳嗽危险性。肾功能状态以及年龄和性别代理的某些生理因素可能对这种关联有一定的效应修饰作用。 |
| English Abstract: |
| Objective To investigate the associations between angiotensin converting enzyme inhibitors (ACEIs) related cough and ACE I/D and bradykinin β 2 receptor (BDKRB2) C/T polymorphism.Methods A case-control study, nested in a 3-year community-based postmarketing surveillance of benazepril in 1 831 Chinese hypertensives was carried out. Three hundred and fifty-one cases having suffered benazepril related cough were identified and genotyped. Genotyped controls were selected through a stratified sampling design by age, sex and kidney function status.Results The allele frequencies in cases were I 65.4%, D 34.6% and T 53.0%, C 47.0% and the genotype frequencies were II 42.2%, ID 46.4%, DD 11.4% (ACE) and CC 21.6%, CT 50.9%, TT 27.6% (BDKRB2), respectively. Genotype frequencies were both in Hardy-Weinberg equilibrium. According to stratified analyses by sex, kidney function status and age, no association was found between BDKRB2 C/T polymorphism and cough. For ACE I/D polymorphism, in men with decompensated kidney function, patients with ID or DD genotype having 4.805 times the risk of those with II genotype in developing cough. In women aged 35 to 49 years with normal or compensated kidney function, the OR of DD genotype was 5.128. No associations were detected in other subgroups. Conclusions It was suggested that kidney function status and some specific characteristics surrogated by age and sex had modified the effect of ACE I/D variant on cough. |
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