Heart failureRelation of β2-Adrenoceptor Haplotype to Risk of Death and Heart Transplantation in Patients With Heart Failure
Section snippets
Patients
Patients ≥18 years with a diagnosis of HF were recruited from Shands Hospital at the University of Florida from May 2000 to August 2002. No screening procedure was required to participate in the study. The patients were followed until February 15, 2005. The exclusion criteria included previous heart transplantation and any condition other than HF that could limit survival, such as cancer or terminal illness with a life expectancy of <6 months. The institutional review board approved the study,
Baseline characteristics
All patients who agreed to participate (n = 247) did participate in this study. Of the 247 patients, 227 had complete genetic and clinical data (Table 2). Other than a significantly lower New York Heart Association functional class (p = 0.02), those with incomplete data were not different from those included in the analysis when compared using the data available. Baseline drug therapy showed high use rates of the drugs that reduce the adverse outcomes in patients with HF. Specifically, 95% of
Discussion
The data from our study suggest that the ADRB2 RQ haplotype may increase the risk of death or heart transplantation in patients with HF. Specifically, possession of 2 copies of the ADRB2 RQ haplotype was associated with an approximately 90% increase in the risk of death or heart transplantation. This effect was seen after adjustment for nongenetic risk factors, including male gender, etiology, New York Heart Association functional class, left ventricular ejection fraction, serum sodium levels,
Acknowledgment
We thank Tara Andrisin and Lindy Taylor for their recruitment assistance and Robert Rantinella, Melanie Potvin, and Amanda Hudson for their genotyping assistance.
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2015, Canadian Journal of CardiologyCardiovascular pharmacogenomics; state of current knowledge and implementation in practice
2015, International Journal of CardiologyCitation Excerpt :Indeed, patients with the combinations of Arg389Arg homozygotes + any Ins322–325Del allele, Gly389 carriers + Ins322–325Ins wild-type homozygotes and Gly389 carriers + Del322–325 carriers, had, respectively, enhanced, intermediate and no therapeutic benefit of bucindolol for six HF clinical end points (including mortality), as compared with placebo [279]. Also, another study of 277 HF patients treated with β-blockers, investigated the association of clinical outcomes and the polymorphisms of ADRB1, ADRB2 and ADRA2C; the results were significant only for ADRB2 such that carriers of two copies of the ADRB2 Arg16Gln27 haplotype, were at higher risk of adverse outcomes [280]. This association was not replicated in another study in which survival of 637 on-metoprolol or on-carvedilol HF patients was not influenced by the polymorphisms or haplotypes in ADRB1, ADRB2 and ADRA2C [281].
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2014, British Journal of AnaesthesiaCitation Excerpt :However, extension of the study and ethnicity-specific analysis suggested that the association was specific for African Americans.31 Moreover, homozygosity for the Gln27 allele was reported to negatively affect outcome in heart failure.32 33 Thus the augmented β2AR function in Gly16Glu27 haplotypes, which results in a greater vasodilatatory response, might be protective in hypertension or heart disease.
Adrenergic-pathway gene variants influence beta-blockerrelated outcomes after acute coronary syndrome in a race-specific manner
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This study was supported by Grant HL68834 from the National Institutes of Health, Bethesda, Maryland, and by Postdoctoral Fellowship Grant 0525474B from the American Heart Association, St. Petersburg, Florida.