TY - JOUR
T1 - Endothelial Nitric Oxide Synthase (NOS3) Polymorphisms in African Americans With Heart Failure
T2 - Results From the A-HeFT Trial
AU - McNamara, Dennis M.
AU - Tam, S. William
AU - Sabolinski, Michael L.
AU - Tobelmann, Page
AU - Janosko, Karen
AU - Venkitachalam, Lakshmi
AU - Ofili, Elizabeth
AU - Yancy, Clyde
AU - Feldman, Arthur M.
AU - Ghali, Jalal K.
AU - Taylor, Anne L.
AU - Cohn, Jay N.
AU - Worcel, Manuel
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Background: Genetic heterogeneity at the endothelial nitric oxide synthase (NOS3) locus influences heart failure outcomes. The prevalence of NOS3 variants differs in black and white cohorts, but the impact of these differences is unknown. Methods and Results: Subjects (n = 352) in the Genetic Risk Assessment of Heart Failure (GRAHF) substudy of the African-American Heart Failure Trial were genotyped for NOS3 polymorphisms: -786 T/C promoter, intron 4a/4b, and Glu298Asp and allele frequencies and compared with a white heart failure cohort. The effect of treatment with fixed-dose combination of isosorbide dinitrates and hydralazine (FDC I/H) on event-free survival and composite score (CS) of survival, hospitalization, and quality of life (QoL) was analyzed within genotype subsets. In GRAHF, NOS3 genotype frequencies differed from the white cohort (P < .001). The -786 T allele was associated with lower left ventricular ejection fraction (LVEF) (P = .01), whereas the intron 4a allele was linked to lower diastolic blood pressure and higher LVEF (P = .03). Only the Glu298Asp polymorphism influenced treatment outcome; therapy with FDC I/H improved CS (P = .046) and QoL (P = .03) in the Glu298Glu subset only. Conclusions: In black subjects with heart failure, NOS3 genotype influences blood pressure and left ventricular remodeling. The impact of genetic heterogeneity on treatment with FDC I/H requires further study.
AB - Background: Genetic heterogeneity at the endothelial nitric oxide synthase (NOS3) locus influences heart failure outcomes. The prevalence of NOS3 variants differs in black and white cohorts, but the impact of these differences is unknown. Methods and Results: Subjects (n = 352) in the Genetic Risk Assessment of Heart Failure (GRAHF) substudy of the African-American Heart Failure Trial were genotyped for NOS3 polymorphisms: -786 T/C promoter, intron 4a/4b, and Glu298Asp and allele frequencies and compared with a white heart failure cohort. The effect of treatment with fixed-dose combination of isosorbide dinitrates and hydralazine (FDC I/H) on event-free survival and composite score (CS) of survival, hospitalization, and quality of life (QoL) was analyzed within genotype subsets. In GRAHF, NOS3 genotype frequencies differed from the white cohort (P < .001). The -786 T allele was associated with lower left ventricular ejection fraction (LVEF) (P = .01), whereas the intron 4a allele was linked to lower diastolic blood pressure and higher LVEF (P = .03). Only the Glu298Asp polymorphism influenced treatment outcome; therapy with FDC I/H improved CS (P = .046) and QoL (P = .03) in the Glu298Glu subset only. Conclusions: In black subjects with heart failure, NOS3 genotype influences blood pressure and left ventricular remodeling. The impact of genetic heterogeneity on treatment with FDC I/H requires further study.
KW - Pharmacogenetics
KW - isosorbide dinitrate and hydralazine
KW - left ventricular ejection fraction
KW - nitric oxide
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U2 - 10.1016/j.cardfail.2008.10.028
DO - 10.1016/j.cardfail.2008.10.028
M3 - Article
C2 - 19327620
AN - SCOPUS:62649122885
VL - 15
SP - 191
EP - 198
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
SN - 1071-9164
IS - 3
ER -