Rs495828 polymorphism of the ABO gene is a predictor of enalapril-induced cough in Chinese patients with essential hypertension

作者：Jian‐Quan Luo, Fazhong He, Zhiying Luo, Jiagen Wen, Luyan Wang, Ningling Sun, Genfu Tang, Qing Li, Dong Guo, Zhaoqian Liu, Hong‐Hao Zhou, Xiaoping Chen, Wei Zhang · 发表于：Pharmacogenetics and Genomics · 年份：2014 · DOI：10.1097/fpc.0000000000000050 · 被引用次数：44 · 研究领域：Respiratory and Cough-Related Research、Asthma and respiratory diseases、Renin-Angiotensin System Studies

OBJECTIVE: ABO genetic polymorphisms have recently been associated with angiotensin-converting enzyme (ACE) activity and inflammation, which play a critical role in the pathogenic mechanism of ACE inhibitor-induced cough. Therefore, the current study determined the association of ABO genetic polymorphisms with enalapril-induced cough in Chinese patients with essential hypertension. METHODS: A total of 450 essential hypertensive patients treated with 10 mg of enalapril maleate were genotyped for ABO genetic polymorphisms using the PCR-direct sequencing method. Cough was recorded when patients were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. RESULTS: The distribution of rs8176740 and rs495828 was different between the coughers and the controls [P=0.039; odds ratio (OR)=0.70, P=0.018; OR=1.41]. The risk of enalapril-induced cough in the rs495828 TT carriers was increased (P=0.008; OR=2.69), which remained significant after false discovery rate correction. The results for the rs8176740 polymorphism were significant in the female subgroup (P=0.027; OR=0.22). Haplotype analysis of the four ABO polymorphisms (rs8176746/rs8176740/rs495828/rs12683493) showed that the frequency of the GATC haplotype was higher in the coughers than those in the controls (26.6 vs. 18.8%, P=0.033; OR=1.43). CONCLUSION: The rs495828 polymorphism was associated with enalapril-induced cough and may serve as a useful pharmacogenomics marker of the safet...