Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Cardiol. Oct 26, 2011; 3(10): 329-336
Published online Oct 26, 2011. doi: 10.4330/wjc.v3.i10.329
Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough: A meta-analysis
Kazuaki Nishio, Shinji Kashiki, Hideaki Tachibana, Youichi Kobayashi
Kazuaki Nishio, Shinji Kashiki, Hideaki Tachibana, Matsui Hospital, The Department of Cardiology, Tokyo, 146-0082, Japan
Kazuaki Nishio, Hideaki Tachibana, Youichi Kobayashi, The Third Department of Internal Medicine, School of Medicine Showa University, Tokyo 142-8666, Japan
Author contributions: Nishio K designed and performed the statistics; Kashiki S, Tachibana H and Kobayashi Y participate in selection of trials and data synthesis.
Correspondence to: Kazuaki Nishio, MD, PhD, The Third Department of Internal Medicine, School of Medicine Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. kazukun@jg7.so-net.ne.jp
Telephone: +81-3-37521111 Fax: +81-3-37521119
Received: February 9, 2011
Revised: July 22, 2011
Accepted: July 29, 2011
Published online: October 26, 2011
Abstract

AIM: To evaluate the association between genetic polymorphisms and angiotensin converting enzyme inhibitor (ACEI)-related cough, and the race- or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.

METHODS: We conducted a search in PubMed, EMBASE, Cinahl, and the Cochrane Database without language limitation. A database of 11 studies on ACEI-related cough, with detailed information regarding ACE I/D or bradykinin B2 receptor polymorphisms, was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. A subgroup analysis was also performed using ethnicity.

RESULTS: Six studies were included on ACE I/D polymorphism (398 Caucasians, 723 East Asians), and three studies were included on bradykinin B2 receptor polymorphism (300 East Asians). The distribution of ACE genotypes showed significant differences in the entire population (P = 0.004) and in East Asians (P = 0.005) but not in Caucasians (P = 0.23). Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR) = 1.49 (1.11-2.02)]. The meta-analysis with a random effects model showed a significant association between ACE allele I/D and ACEI-related cough [random effects (RE) OR = 1.49 (1.11-2.02), P = 0.009] in East Asians, but not in Caucasians [RE OR = 0.90 (0.60-1.35)]. The allelic frequencies of the bradykinin B2 receptor gene were significantly different [OR = 2.25 (1.42-3.57)]. The distributions of the T/C genotypes of the bradykinin B2 receptor gene were significantly different (χ2 = 8.366, P = 0.015). The meta-analyses revealed that there was a significant association between the bradykinin B2 receptor allele and ACEI-related cough in East Asians [RE OR = 2.29 (1.42-3.69), P = 0.001].

CONCLUSION: ACE I/D and Bradykinin B2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians, but a negative association between ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Keywords: Angiotensin converting enzyme inhibitor; Bradykinin; Cough; Genes; Polymorphism