Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin-converting enzyme inhibitor-induced cough

Abstract

Background and objective: Treatment with angiotensin-converting enzyme (ACE) inhibitors can induce chronic cough in many patients. Genetic variations in the neurokinin 2 receptor gene (NK2R) are significantly associated with cough sensitivity to capsaicin. Methods: This study assessed the relationship between genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking ACE inhibitors. Patients included in the study did not have chest abnormalities, postnasal drip, gastroesophageal reflux or a recent history of upper respiratory infection. Results: We detected two single nucleotide polymorphisms in the NK2R gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231 were 36 center dot 3% for Gly/Gly, 49 center dot 5% for Gly/Glu and 14 center dot 3% for Glu/Glu. The allelic frequencies at amino acid 375 were 74 center dot 7% for Arg/Arg, 24 center dot 2% for Arg/His and 1 center dot 1% for His/His. The prevalence of chronic cough in patients with the amino acid 231 genotype was 33 center dot 3% in Gly/Gly homozygotes, 24 center dot 4% in Gly/Glu heterozygotes and 0% in Glu/Glu homozygotes. There was a statistically significant association between chronic cough and the Glu/Glu allele (P = 0 center dot 028) when the data were analyzed with a recessive model. In addition, there was a significant inverse linear association between the number of Glu231 alleles and ACE inhibitor-related cough (P = 0 center dot 026). The prevalence of chronic cough in patients with the amino acid 375 genotype was 22 center dot 1% in Arg/Arg homozygotes, 31 center dot 8% in Arg/His heterozygotes and 0% in His/His homozygotes, although none of these association were statistically significant. Conclusion: Our findings indicate that the Gly231Glu polymorphism is associated with a lower prevalence of ACE inhibitor-related cough.