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Pharmacogenomic Ass...
Pharmacogenomic Association of Nonsynonymous SNPs in SIGLEC12, A1BG, and the Selectin Region and Cardiovascular Outcomes
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McDonough, Caitrin W. (författare)
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Gong, Yan (författare)
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Padmanabhan, Sandosh (författare)
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Burkley, Ben (författare)
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Langaee, Taimour Y. (författare)
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- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Pepine, Carl J. (författare)
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Dominiczak, Anna F. (författare)
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Cooper-DeHoff, Rhonda M. (författare)
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Johnson, Julie A. (författare)
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(creator_code:org_t)
- 2013
- 2013
- Engelska.
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Ingår i: Hypertension. - 1524-4563. ; 62:1, s. 48-54
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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)
Nyckelord
- antihypertensive agents
- -blockers
- calcium channel blockers
- genetic
- variation
- hypertension
- pharmacogenetics
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- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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McDonough, Caitr ...
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Gong, Yan
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Padmanabhan, San ...
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Burkley, Ben
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Langaee, Taimour ...
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Melander, Olle
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visa fler...
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Pepine, Carl J.
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Dominiczak, Anna ...
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Cooper-DeHoff, R ...
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Johnson, Julie A ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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Hypertension
- Av lärosätet
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Lunds universitet