Specific SNPs in the angiotensinogen, apolipoprotein B, and alpha2 adrenoreceptor genes significantly predicted the change in left ventricular mass during 12 weeks of antihypertensive therapy.
RCT (n=97)
Double-blind
Do single nucleotide polymorphisms predict the change in left ventricular mass index in patients with hypertension and LV hypertrophy treated with irbesartan or atenolol?
Specific single nucleotide polymorphisms can predict the regression of left ventricular hypertrophy in response to specific antihypertensive medications, highlighting the potential for pharmacogenomic tailoring of therapy.
BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.
Liljedahl et al. (Wed,) conducted a rct in mild to moderate primary hypertension and left ventricular hypertrophy (n=97). Irbesartan vs. Atenolol was evaluated on change in left ventricular mass index. Specific SNPs in the angiotensinogen, apolipoprotein B, and alpha2 adrenoreceptor genes significantly predicted the change in left ventricular mass during 12 weeks of antihypertensive therapy.