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Angiotensin\u2010converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with the responses to ACEi. We examined whether <jats:italic>PRKCA<\/jats:italic> (protein kinase C, alpha) polymorphisms (rs887797 C&gt;T, rs1010544 T&gt;C and rs16960228 G&gt;A), or haplotypes, and gene\u2013gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with enalapril as monotherapy. Patients were classified as poor responders (PR) or good responders (GR) to enalapril if their changes in mean arterial pressure were lower or higher than the median value, respectively. Multi\u2010factor dimensionality reduction was used to characterize interactions among <jats:italic>PRKCA<\/jats:italic>,<jats:italic> NOS3<\/jats:italic> (nitric oxide synthase 3) and <jats:italic>BDKRB2<\/jats:italic> (bradykinin receptor B2) polymorphisms. The TC+CC genotypes for the rs1010544 polymorphism were more frequent in GR than in PR (<jats:italic>p<\/jats:italic> = 0.037). Conversely, the GA+AA genotypes for the rs16960228 polymorphism, and the CTA haplotype, were more frequent in PR than in GR (<jats:italic>p<\/jats:italic> = 0.040 and <jats:italic>p<\/jats:italic> = 0.008, respectively). Moreover, the GG genotype for the <jats:italic>PRKCA<\/jats:italic> rs16960228 polymorphism was associated with PR or GR depending on the genotypes for the rs2070744 (<jats:italic>NOS3<\/jats:italic>) and rs1799722 (<jats:italic>BDKRB2<\/jats:italic>) polymorphisms (<jats:italic>p<\/jats:italic> = 0.012). Our results suggest that <jats:italic>PRKCA<\/jats:italic> polymorphisms and gene\u2013gene interactions within the ACEi pathway affect the antihypertensive responses to enalapril.<\/jats:p>","DOI":"10.1111\/bcpt.12682","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T12:38:19Z","timestamp":1475843899000},"page":"284-291","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Gene\u2013Gene Interactions Among <i>PRKCA<\/i>,<i> NOS3<\/i> and <i>BDKRB2<\/i> Polymorphisms Affect the Antihypertensive Effects of Enalapril"],"prefix":"10.1111","volume":"120","author":[{"given":"Gustavo H.","family":"Oliveira\u2010Paula","sequence":"first","affiliation":[{"name":"Department of Pharmacology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo 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