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Sökning: onr:"swepub:oai:lup.lub.lu.se:1322eb9d-be3b-4bda-bf1b-d538eb9ebf94" > Pharmacogenomic Ass...

Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes

McDonough, Caitrin W. (författare)
Gong, Yan (författare)
Padmanabhan, Sandosh (författare)
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Burkley, Ben (författare)
Langaee, Taimour Y. (författare)
Melander, Olle (författare)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Pepine, Carl J. (författare)
Dominiczak, Anna F. (författare)
Cooper-DeHoff, Rhonda M. (författare)
Johnson, Julie A. (författare)
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 (creator_code:org_t)
Lippincott Williams & Wilkins, 2013
2013
Engelska.
Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 1524-4563. ; 62:1, s. 48-54
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)xtreatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39x10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

antihypertensive agents
-blockers
calcium channel blockers
genetic
variation
hypertension
pharmacogenetics

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