Single nucleotide polymorphisms predict the change in left ventricular mass in response to anti hypertensive treatment

Background Our aim was to determine whether the change in left ventricular (LV) mass in response to anti hypertensive 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 beta(1) 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, corrsponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha(2A) 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 alpha(2) adrenoreceptor gene predicted the change in LV mass during anti hypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses. (C) 2004 Lippincott Williams Wilkins.