Polymorphisms of the XXXX predict exercise capacity in @entity712 .

@entity1 @entity1522 @entity712 @entity296 @entity2162 @entity4962 @entity308 @entity26 @entity4022 @entity2161 @entity534 @entity3762
BACKGROUND: Exercise performance in @entity1 with @entity712 is partially dependent on cardiac @entity2161 ( @entity2161 ) function. There are 2 common polymorphisms of the @entity2161 gene that alter the encoded @entity1522 at positions 49 (Ser or @entity4022 ) and 389 ( @entity4022 or @entity534 ) and alter receptor function in vitro. Their relevance to modification of cardiac function in @entity712 is not known. METHODS: Exercise testing was performed in 263 @entity1 with @entity3762 or @entity296 (left ventricular ejection fraction approximately 25%). Potential associations were sought between @entity2161 genotypes and the primary outcome variables of peak @entity26 consumption (VO2), heart rate response, and exercise time. RESULTS: The major determinants of exercise capacity were the polymorphisms at position 389, where @entity1 homozygous for @entity4022 389 had significantly lower peak VO2 compared with those with @entity534 389 (14.5 +/- 0.6 vs 17.7 +/- 0.4 mL/kg/min, P =.006), despite similar clinical characteristics including left ventricular ejection fraction. Consistent with a gene dose-response, heterozygosity was associated with an intermediate response (16.9 +/- 0.6 mL/kg/min, P <.05). When position 49 genotypes were included, a graded relationship between the 5 2-locus haplotypes and VO2 was found. Two haplotypes displayed the most divergent peak @entity4962 : homozygous @entity4022 389/Ser49, and homozygous @entity534 389/Gly49 carriers (14.4 +/- 0.5 vs 18.2 +/- 0.8 mL/kg/min, P =.001). Genotype did not predict the heart rate response. The above results were independent of beta-blocker or other medication use, left ventricular ejection fraction, @entity2162 genotype, or other demographic and clinical characteristics. CONCLUSION: @entity2161 polymorphisms are a significant determinant of exercise capacity in @entity1 with @entity712 . Early identification, by genetic testing for these polymorphisms, of @entity712 @entity1 at risk for development of @entity308 exercise capacity may be useful for initiation of specific therapy tailored to genotype.
