title: Pharmacogenetic implications for eight common blood pressure-associated single-nucleotide polymorphisms.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Norway. Viktor.Hamrefors@med.lu.se
authors.forename: Viktor
authors.initials: V
authors.lastname: Hamrefors
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Björn
authors.initials: B
authors.lastname: Wahlstrand
authors.forename: Sverre
authors.initials: S
authors.lastname: Kjeldsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Hedner
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013548:Sweden
chemical_list: D000959:Antihypertensive Agents