Literature DB >> 22543981

Pharmacogenetics and healthcare outcomes in patients with chronic heart failure.

Kye-Min Kim1, Michael D Murray, Wanzhu Tu, Jason Robarge, Yan Ding, D Craig Brater, David A Flockhart.   

Abstract

PURPOSE: To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, such as medication adherence.
METHODS: One year-hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older. Medication adherence was measured. Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes. The genotypes of polymorphisms in six genes were determined: α(2C)-AR (ADRA2C), β₁-AR (ADRB1), β₂-AR (ADRB2), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and CYP4A11. Haplotypes for ADRB1 and ADRB2 were estimated. The genotype effects on healthcare outcomes were examined using log-linear regression models.
RESULTS: Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01-0.54, P = 0.022]. Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09-0.59, P = 0.006). Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively. For ADRB2, the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers (P < 0.05). Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01-0.25, P = 0.0013 and IRR 0.10, 95 % CI 0.02-0.42, P = 0.006, respectively). The other polymorphisms showed no association with healthcare outcomes.
CONCLUSIONS: After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1, ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.

Entities:  

Mesh:

Substances:

Year:  2012        PMID: 22543981     DOI: 10.1007/s00228-012-1280-z

Source DB:  PubMed          Journal:  Eur J Clin Pharmacol        ISSN: 0031-6970            Impact factor:   2.953


  32 in total

Review 1.  Nitric oxide synthases in the failing human heart: a doubled-edged sword?

Authors:  H Drexler
Journal:  Circulation       Date:  1999-06-15       Impact factor: 29.690

2.  Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension.

Authors:  James V Gainer; Aouatef Bellamine; Elliott P Dawson; Kristie E Womble; Sarah W Grant; Yarong Wang; L Adrienne Cupples; Chao-Yu Guo; Serkalem Demissie; Christopher J O'Donnell; Nancy J Brown; Michael R Waterman; Jorge H Capdevila
Journal:  Circulation       Date:  2004-12-20       Impact factor: 29.690

3.  A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors.

Authors:  K M Small; S L Forbes; F F Rahman; K M Bridges; S B Liggett
Journal:  J Biol Chem       Date:  2000-07-28       Impact factor: 5.157

4.  Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome.

Authors:  David E Lanfear; Philip G Jones; Sharon Marsh; Sharon Cresci; Howard L McLeod; John A Spertus
Journal:  JAMA       Date:  2005-09-28       Impact factor: 56.272

5.  A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor.

Authors:  D A Mason; J D Moore; S A Green; S B Liggett
Journal:  J Biol Chem       Date:  1999-04-30       Impact factor: 5.157

6.  Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants.

Authors:  J E Tanus-Santos; M Desai; D A Flockhart
Journal:  Pharmacogenetics       Date:  2001-11

7.  Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking.

Authors:  Deborah A Rathz; Kari M Brown; Lisa A Kramer; Stephen B Liggett
Journal:  J Cardiovasc Pharmacol       Date:  2002-02       Impact factor: 3.105

8.  A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese.

Authors:  M Yoshimura; H Yasue; M Nakayama; Y Shimasaki; H Sumida; S Sugiyama; K Kugiyama; H Ogawa; Y Ogawa; Y Saito; Y Miyamoto; K Nakao
Journal:  Hum Genet       Date:  1998-07       Impact factor: 4.132

9.  Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure.

Authors:  Dennis M McNamara; Richard Holubkov; Lisa Postava; Ravi Ramani; Karen Janosko; Michael Mathier; Guy A MacGowan; Srinivas Murali; Arthur M Feldman; Barry London
Journal:  Circulation       Date:  2003-03-17       Impact factor: 29.690

10.  A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.

Authors:  K Lindpaintner; M A Pfeffer; R Kreutz; M J Stampfer; F Grodstein; F LaMotte; J Buring; C H Hennekens
Journal:  N Engl J Med       Date:  1995-03-16       Impact factor: 91.245

View more
  6 in total

Review 1.  Practical Pharmacogenomic Approaches to Heart Failure Therapeutics.

Authors:  Chayakrit Krittanawong; Amalia Namath; David E Lanfear; W H Wilson Tang
Journal:  Curr Treat Options Cardiovasc Med       Date:  2016-10

Review 2.  Pharmacogenomics in heart failure: where are we now and how can we reach clinical application?

Authors:  Akinyemi Oni-Orisan; David E Lanfear
Journal:  Cardiol Rev       Date:  2014 Sep-Oct       Impact factor: 2.644

Review 3.  Pharmacogenetic factors affecting β-blocker metabolism and response.

Authors:  Cameron D Thomas; Julie A Johnson
Journal:  Expert Opin Drug Metab Toxicol       Date:  2020-09-09       Impact factor: 4.481

4.  The undiscovered country: the future of integrating genomic information into the EHR.

Authors:  Joseph L Kannry; Marc S Williams
Journal:  Genet Med       Date:  2013-09-26       Impact factor: 8.822

5.  Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.

Authors:  Cameron D Thomas; Scott A Mosley; Sarah Kim; Karthik Lingineni; Nihal El Rouby; Taimour Y Langaee; Yan Gong; Danxin Wang; Siegfried O Schmidt; Philip F Binkley; David S Estores; Kairui Feng; Hyewon Kim; Minori Kinjo; Zhichuan Li; Lanyan Fang; Arlene B Chapman; Rhonda M Cooper-DeHoff; John G Gums; Issam S Hamadeh; Liang Zhao; Stephan Schmidt; Reginald F Frye; Julie A Johnson; Larisa H Cavallari
Journal:  CPT Pharmacometrics Syst Pharmacol       Date:  2020-11-03

6.  A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management.

Authors:  Julie A Johnson; Larisa H Cavallari; Cameron D Thomas; Hari K Parvataneni; Chancellor F Gray; Justin T Deen; Hernan A Prieto; Luis F Pulido; Amanda R Elsey; Erica N Elwood; Petr Starostik; Yan Gong; Roger B Fillingim
Journal:  Genet Med       Date:  2021-01-08       Impact factor: 8.822

  6 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.