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Sökning: WFRF:(Donner Kati M)

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1.
  • Chittani, Martina, et al. (författare)
  • TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.
  • 2015
  • Ingår i: Journal of Hypertension. - 1473-5598. ; 33:6, s. 1301-1309
  • Tidskriftsartikel (refereegranskat)abstract
    • Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
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2.
  • Turner, Stephen T., et al. (författare)
  • Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
  • 2013
  • Ingår i: Hypertension. - 1524-4563. ; 62:2, s. 391-397
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes influencing blood pressure response to thiazide diuretic therapy for hypertension, we conducted genome-wide association meta-analyses of approximate to 1.1 million single-nucleotide polymorphisms in a combined sample of 424 European Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=228) and the Genetic Epidemiology of Responses to Antihypertensive study (n=196). Polymorphisms associated with blood pressure response at P<10(-5) were tested for replication of the associations in independent samples of hydrochlorothiazide-treated European hypertensives. The rs16960228 polymorphism in protein kinase C, replicated for same-direction association with diastolic blood pressure response in the Nordic Diltiazem study (n=420) and the Genetics of Drug Responsiveness in Essential Hypertension study (n=206), and the combined 4-study meta-analysis P value achieved genome-wide significance (P=3.3x10(-8)). Systolic or diastolic blood pressure responses were consistently greater in carriers of the rs16960228 A allele than in GG homozygotes (>4/4 mm Hg) across study samples. The rs2273359 polymorphism in the GNAS-EDN3 region also replicated for same-direction association with systolic blood pressure response in the Nordic Diltiazem study, and the combined 3-study meta-analysis P value approached genome-wide significance (P=5.5x10(-8)). The findings document clinically important effects of genetic variation at novel loci on blood pressure response to a thiazide diuretic, which may be a basis for individualization of antihypertensive drug therapy and identification of new drug targets.
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