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A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.
Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Velez Edwards, D R; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C N A; Doney, A; MahmoudPour, S H; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M.
Afiliação
  • Mosley JD; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Shaffer CM; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Van Driest SL; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Weeke PE; Department of Pediatrics, Vanderbilt University, Nashville, TN, USA.
  • Wells QS; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Karnes JH; Department of Cardiology, Copenhagen University, Copenhagen, Denmark.
  • Velez Edwards DR; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Wei WQ; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Teixeira PL; Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
  • Bastarache L; Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
  • Crawford DC; Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
  • Li R; Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
  • Manolio TA; Department of Epidemiology and Biostatistics; Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
  • Bottinger EP; Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD, USA.
  • McCarty CA; Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD, USA.
  • Linneman JG; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Brilliant MH; Essentia Institute of Rural Health, Duluth, MN, USA.
  • Pacheco JA; Marshfield Clinic Research Foundation, Marshfield, WI, USA.
  • Thompson W; Marshfield Clinic Research Foundation, Marshfield, WI, USA.
  • Chisholm RL; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Jarvik GP; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Crosslin DR; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Carrell DS; Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA.
  • Baldwin E; Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA.
  • Ralston J; Group Health Research Institute, Seattle, WA, USA.
  • Larson EB; Group Health Research Institute, Seattle, WA, USA.
  • Grafton J; Group Health Research Institute, Seattle, WA, USA.
  • Scrol A; Group Health Research Institute, Seattle, WA, USA.
  • Jouni H; Group Health Research Institute, Seattle, WA, USA.
  • Kullo IJ; Group Health Research Institute, Seattle, WA, USA.
  • Tromp G; Division of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA.
  • Borthwick KM; Division of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA.
  • Kuivaniemi H; The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
  • Carey DJ; The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
  • Ritchie MD; The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
  • Bradford Y; The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
  • Verma SS; Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
  • Chute CG; Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
  • Veluchamy A; Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
  • Siddiqui MK; Schools of Medicine, Public Health, and Nursing, Johns Hopkins University, Baltimore, MD, USA.
  • Palmer CN; Medical Research Institute, University of Dundee, Dundee, UK.
  • Doney A; Medical Research Institute, University of Dundee, Dundee, UK.
  • MahmoudPour SH; Medical Research Institute, University of Dundee, Dundee, UK.
  • Maitland-van der Zee AH; Medical Research Institute, University of Dundee, Dundee, UK.
  • Morris AD; Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
  • Denny JC; Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
  • Roden DM; School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Pharmacogenomics J ; 16(3): 231-7, 2016 06.
Article em En | MEDLINE | ID: mdl-26169577
ABSTRACT
The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI) 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 Base de dados: MEDLINE Assunto principal: Inibidores da Enzima Conversora de Angiotensina / Tosse / Polimorfismo de Nucleotídeo Único / Proteínas Interatuantes com Canais de Kv Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: America do norte / Europa Idioma: En Revista: Pharmacogenomics J Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 Base de dados: MEDLINE Assunto principal: Inibidores da Enzima Conversora de Angiotensina / Tosse / Polimorfismo de Nucleotídeo Único / Proteínas Interatuantes com Canais de Kv Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: America do norte / Europa Idioma: En Revista: Pharmacogenomics J Ano de publicação: 2016 Tipo de documento: Article