Frequency of compound genotypes associated with beta-blocker efficacy in congestive heart failure.

An important practical problem in pharmacogenetics is the integration of compound genotypes into individualized therapy. Polymorphisms in the genes encoding the angiotensin-converting enzyme, and beta(1)- and beta(2)-adrenoceptors have been identified as predictors of 'good response' to beta-adrenergic antagonists among heart failure patients. These variants were used as the basis for exploring the concept of compound genotype assessment. The frequency of compound variants in these genes was determined using PCR and pyrosequencing to genotype population samples of 95 African-Americans and 95 European-Americans. Both groups could be divided into four subgroups according to the number of favorable genotypes present. Each subgroup accounted for a significant proportion of subjects (the smallest was 7% of total). This study provides the first look into the population frequency of these compound genotypes, and it provides the necessary first step for future evaluation of polygenic strategies to individualize therapy for heart failure.