Abstract 2178: Adrenoceptor α1B (G549A) and Norepinephrine Transporter (T-182C) Polymorphisms are Associated with the Response to β-Blockers in the Patients with Dilated Cardiomyopathy
Background: Recent clinical trials have clearly demonstrated that the blockade of adrenergic β-receptor decreases the mortality in the patients with chronic heart failure (CHF). Approximately 60% of CHF patients exhibit the improvement of left ventricular function in response to β-blockers, but the others (about 40%) show poor prognosis without beneficial responses.
Aim: To address this inter-individual variability of the response to β-blockers, we investigated the associations between the response and genetic polymorphisms in 16 genes related to adrenergic system.
Methods: Patients with CHF due to dilated cardiomyopathy (n=80) were genotyping by PCR-based methods. We defined good response to β-blockers as the improvement of left ventricular fractional shortening (LVFS) by 5%, examined by echocardiography. Multivariate logistic regression analysis with adjustment for age, sex, LVFS and NYHA class at pre-administration was performed to evaluate associations between the response to β-blockers and each polymorphisms. To reduce the type I error derived from multiple testing, p<0.01 was considered to be significant.
Results: Baseline LVFS and NYHA class were statistically different between responder and non-responder groups. Adrenoceptor α1B (ADRA1B) G549A (non-responder%; GG 53.3%, GA 37.8%, AA 15.4%, p=0.005) and norepinephrine transporter (NET) T-182C (non-responder%; TT 25.9%, TC 39.0%, CC 75.0%, p=0.007) were associated with response to β-blockers. Finally, we scored the risk for non-responders, according to the formula for prediction of β-blocker response (Table⇓). About 79% of the patients with more than 0.5 were found to be non-responders, while 81% of the remainders were responders.
Conclusion: ADRA1B (G549A) and NET (T-182C) polymorphisms are independent predictors of the response to β-blockers. These pharmacogenomic findings may be helpful in individualized medicine of β-blockers in CHF.