| Pharmacogenetic predictors of angiotensin-converting enzyme inhibitor-induced cough: the role of ACE, ABO, and BDKRB2 genes. | |
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MedLine Citation:
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PMID: 21832968 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND AND OBJECTIVE: Dry cough is the most common reason for stopping angiotensin-converting enzyme inhibitors (ACEi) therapy. The role of ACE in the metabolism of bradykinin has been proposed as a pathogenic mechanism. This study included a complete analysis of the variability of the genes involved in bradykinin metabolism (ACE and XPNPEP2) and bradykinin receptors (BDKRB2). We included two polymorphisms in the ABO (related to ACE levels); two polymorphisms in the AGTR1, and one polymorphism in the BKRB1 (related to ACEi response). METHODS: A total of 281 patients who had been treated with ACEi were retrospectively recruited [102 patients were considered as cases (cough) and 179 patients were considered as controls (no cough)], and 56 polymorphisms were tested for association. RESULTS: We found that genetic polymorphisms in BDKRB2 [rs8016905; P=0.003; odds ratio (OR)=2.21] and ABO (rs495828; P=0.001; OR=2.45) are associated with ACEi-induced cough after correction for multiple testing. The effect of polymorphisms in ABO was sex specific (female patients; P=0.0006; OR=3.26). When we analyzed the subgroup of patients homozygous GG for rs4343, two polymorphisms in the ACE were found to have protective properties (rs4459610 and rs4267385; P=0.005 and 0.004; OR=0.25). We also found a strong interaction between the ABO polymorphisms, rs495828 and rs8176746 (P<0.0001; OR=3.7). CONCLUSION: These results highlight the importance of genetic determinants of ACE levels as good predictors of the ACEi response, and provide ABO as a good candidate gene for pharmacogenetic studies of ACEi-related cough. Moreover, our results also confirm the importance of bradykinin in the pathogenesis of this adverse effect. |
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Authors:
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Sergi Mas; Patricia Gassò; Santiago Alvarez; Jacint Ortiz; Jose M Sotoca; Antonio Francino; Xavier Carne; Amalia Lafuente |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Pharmacogenetics and genomics Volume: 21 ISSN: 1744-6880 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101231005 Medline TA: Pharmacogenet Genomics Country: United States |
Other Details:
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Languages: eng Pagination: 531-8 Citation Subset: IM |
Affiliation:
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aDepartments of Anatomic Pathology, Pharmacology, and Microbiology, University of Barcelona bPrimary Care Center Les Corts, Corporacio Sanitaria Clínic cPharmacy Service dDepartment of Cardiology, Thorax Institute eClinical Pharmacology Service, Hospital Clinic, Barcelona fInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona gCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. |
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