Lee Y J, Tsai J C
Department of Clinical Research, Ping-Tung Christian Hospital, Ping-Tung, Taiwan, Republic of China.
Metabolism. 2001 Nov;50(11):1346-50. doi: 10.1053/meta.2001.27212.
To investigate the genetic susceptibility associated with cough related to angiotensin-converting enzyme inhibitor (ACEI) therapy in patients with type 2 diabetes, 189 non-insulin-dependent diabetes mellitus (NIDDM) patients with proteinuria or hypertension treated with perindopril were studied. Cough was considered to be present if the patients had been bothered by a cough during treatment and if they had had related symptoms for at least 2 weeks without an identifiable cause. Polymerase chain reaction (PCR) coupled with single-strand conformation polymorphism (SSCP) was used to detect polymorphisms of ACE and bradykinin B2-receptor genes. After 8 weeks of treatment, 49.2% (93 of 189) of our NIDDM patients were found to be suffering from ACEI-related cough. ACEI-related cough was mainly associated with female patients, with 71.7% (76 of 106) of female and only 20.5% (17 of 83) of male patients experiencing cough after ACEI treatment. There was a significant association of ACE II genotype with ACEI-related cough. The genotype frequencies were 58.2% for II, 47.8% for ID, and 16.7% for DD in patients with ACEI-associated cough and 41.8% for II, 52.2% for ID, and 83.3% for DD in subjects without ACEI-associated cough (chi(2) = 10.268; df = 2, P =.006). As female patients made up the majority of the subjects suffering from ACEI-related cough, we further analyzed the association of ACE I/D genotype with ACEI-related cough separately by sex. Male patients with ACEI-related cough were not associated with ACE I/D genotype distribution, while female patients were strongly associated with ACE I/D genotype polymorphism (chi(2) = 16.12; df = 2; P <.001). There was no association between the bradykinin B2 receptor gene -58T/C polymorphism with ACEI-related cough. In conclusion, our results indicate that Chinese diabetic female subjects are susceptible to ACEI-related cough, and this susceptibility may be genetically predetermined.
为研究2型糖尿病患者中与血管紧张素转换酶抑制剂（ACEI）治疗相关咳嗽的遗传易感性，我们对189例接受培哚普利治疗的伴有蛋白尿或高血压的非胰岛素依赖型糖尿病（NIDDM）患者进行了研究。如果患者在治疗期间受到咳嗽困扰且有相关症状至少2周且无明确病因，则认为存在咳嗽。采用聚合酶链反应（PCR）结合单链构象多态性（SSCP）检测ACE和缓激肽B2受体基因的多态性。治疗8周后，我们发现49.2%（189例中的93例）的NIDDM患者患有与ACEI相关的咳嗽。与ACEI相关的咳嗽主要与女性患者相关，ACEI治疗后71.7%（106例中的76例）的女性患者出现咳嗽，而男性患者仅20.5%（83例中的17例）出现咳嗽。ACE II基因型与ACEI相关咳嗽存在显著关联。在有ACEI相关咳嗽的患者中，II基因型频率为58.2%，ID基因型频率为47.8%，DD基因型频率为16.7%；在无ACEI相关咳嗽的受试者中，II基因型频率为41.8%，ID基因型频率为52.2%，DD基因型频率为83.3%（χ2 = 10.268；自由度 = 2，P = 0.006）。由于女性患者占患有ACEI相关咳嗽受试者的大多数，我们进一步按性别分别分析了ACE I/D基因型与ACEI相关咳嗽的关联。患有ACEI相关咳嗽的男性患者与ACE I/D基因型分布无关，而女性患者与ACE I/D基因型多态性密切相关（χ2 = 16.12；自由度 = 2；P < 0.001）。缓激肽B2受体基因 -58T/C多态性与ACEI相关咳嗽之间无关联。总之，我们的结果表明中国糖尿病女性受试者易患与ACEI相关的咳嗽，且这种易感性可能是由基因预先决定的。
