Abstract 2821: The Microsatellite Polymorphism of Heme Oxygenase-1 and its Influence on Heart Failure in African American Patients: Implications for the Results of the African American Heart Failure Trial
Introduction: A loss of heme oxygenase (HO-1) activity increases susceptibility to oxidative damage and has been associated with cardiovascular disease. Transcriptional activity of HMOX1, the gene encoding HO-1, is reduced by a promoter microsatellite polymorphism. This study examined the frequency of the HMOX1 microsatellite polymorphism in African American (AA) subjects with and without congestive heart failure (CHF) to further examine mechanisms proposed to explain the African American Heart Failure Trial (A-He-FT) results.
Hypothesis: The HMOX1 polymorphism is more prevalent in the AA population, which may render this population susceptible to oxidant stress and the onset and progression of cardiovascular diseases that are promoted by oxidant mediated mechanisms.
Results: Sequence analysis was performed on 281 CHF patients and 256 controls. The frequency of the HMOX1 polymorphism in the CHF population is shown in the table⇓. Logistic regression revealed a greater odds ratio for AA subjects to have the LL genotype, but this is seen to an even greater extent in those subjects having CHF (P-value = 0.01, OR = 2.26, CI = 1.19 – 4.29).
Conclusions: The A-HeFT results suggested that the benefit of the combination of hydralazine and isosorbide dinitrate in AA subjects was in part due to the antioxidant actions of hydralazine. Our study suggests that the greater prevalence of the LL microsatellite polymorphism in AA patients may contribute to the pathophysiology of CHF owing to a reduced capacity to protect against oxidative stress, and may provide a genomic basis for superior therapies in this population, such as the use of hydralazine and isosorbide dinitrate.