Pharmacogenetic implications for eight common blood pressure-associated single-nucleotide polymorphisms

Abstract

We aimed to test whether eight common recently identified single-nucleotide polymorphisms (SNPs), strongly associated with blood pressure (BP) in the population, also have impact on the degree of BP reduction by antihypertensive agents with different mechanisms. In 3863 Swedish hypertensive patients, we related number of unfavorable alleles of each SNP (i.e. alleles associated with higher baseline BP) to the magnitude of BP reduction during 6 months of monotherapy with either a beta-blocker, a thiazide diuretic or diltiazem. For six SNPs (rs16998073, rs1378942, rs3184504, rs1530440, rs16948048, rs17367504) no pharmacogenetic interactions were suggested, whereas two SNPs showed nominal evidence of association with treatment response: PLCD3-rs12946454 associated with more SBP (beta = 1.53 mmHg per unfavorable allele; P = 0.010) and DBP (beta = 0.73 mmHg per unfavorable allele; P = 0.014) reduction in patients treated with diltiazem, in contrast to those treated with beta-blockers or diuretics wherein no treatment response association was found. CYP17A1-rs11191548 associated with less DBP reduction (beta = -1.26 mmHg per unfavorable allele; P = 0.018) in patients treated with beta-blockers or diuretics, whereas there was no treatment response association in diltiazem-treated patients. However, if accounting for multiple testing, the significant associations for rs12946454 and rs11191548 were attenuated. For a majority of these, eight recently identified BP-associated SNPs, there are probably no important pharmacogenetic interactions for BP reduction with use of beta-blockers, diuretics or diltiazem. Whether the nominally significant associations for rs12946454 and rs11191548 are true signals and could be of possible clinical relevance for deciding treatment of polygenic essential hypertension should be further tested.