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The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension.

Wahlstrand, Björn; Orho-Melander, Marju LU ; Delling, Lotta; Kjeldsen, Sverre; Narkiewicz, Krzysztof; Almgren, Peter LU ; Hedner, Thomas and Melander, Olle LU (2009) In Journal of Hypertension 27(4). p.769-773
Abstract
OBJECTIVE: We tested whether two single-nucleotide polymorphisms (SNPs) (rs2383207 and rs10757278), previously strongly associated with myocardial infarction, are independently associated with stroke and coronary events in patients with hypertension. METHODS: The Nordic Diltiazem study compared the effects of calcium antagonist and beta-blocker or diuretic-based antihypertensive treatment on cardiovascular events in 10 881 patients with hypertension, of whom 5262 patients provided DNA for the present study. We related SNPs rs2383207 and rs10757278 to stroke and to myocardial infarction and coronary revascularizations (coronary events) using crude and multivariate adjusted Cox proportional hazards models. RESULTS: The G-allele of both SNPs... (More)
OBJECTIVE: We tested whether two single-nucleotide polymorphisms (SNPs) (rs2383207 and rs10757278), previously strongly associated with myocardial infarction, are independently associated with stroke and coronary events in patients with hypertension. METHODS: The Nordic Diltiazem study compared the effects of calcium antagonist and beta-blocker or diuretic-based antihypertensive treatment on cardiovascular events in 10 881 patients with hypertension, of whom 5262 patients provided DNA for the present study. We related SNPs rs2383207 and rs10757278 to stroke and to myocardial infarction and coronary revascularizations (coronary events) using crude and multivariate adjusted Cox proportional hazards models. RESULTS: The G-allele of both SNPs predicted coronary events in crude recessive models [hazard ratios = 1.36, 95% confidence interval (CI) = 1.04-1.79, P = 0.02 for rs10757278 and hazard ratios = 1.40, 95% CI = 1.08-1.81, P = 0.01 for rs2383207] as well as after adjustment for classical cardiovascular risk factors. The G-allele of both SNPs predicted incident stroke in crude additive models [rs2383207 hazard ratios = 1.25 (95% CI = 1.02-1.53), P = 0.04 and rs10757278 hazard ratios = 1.34 (95% CI = 1.09-1.65), P = 0.006], as well as after adjustment for classical cardiovascular risk factors and after additional adjustment for prevalent and incident coronary events, atrial fibrillation, ischemic heart disease and congestive heart failure. As was the case for coronary events, the excess genetic risk of stroke was driven by subjects homozygous for the risk allele. CONCLUSION: Genetic variation at the CDKN2A/CDKN2B locus predicts stroke in hypertensive patients. The genetic association with stroke is independent of classical cardiovascular risk factors and of all prevalent and incident coronary events, suggesting that gene variation at this locus promotes either atherosclerosis or another disease mechanism that is common to both coronary and cerebrovascular disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Hypertension
volume
27
issue
4
pages
769 - 773
publisher
Lippincott Williams & Wilkins
external identifiers
  • WOS:000265455800016
  • PMID:19293724
  • Scopus:67649657744
ISSN
1473-5598
DOI
10.1097/HJH.0b013e328326f7eb
language
English
LU publication?
yes
id
86740f30-b88d-4589-a11b-905a16f7e448 (old id 1367700)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19293724?dopt=Abstract
date added to LUP
2009-04-08 13:07:10
date last changed
2016-11-20 04:21:18
@misc{86740f30-b88d-4589-a11b-905a16f7e448,
  abstract     = {OBJECTIVE: We tested whether two single-nucleotide polymorphisms (SNPs) (rs2383207 and rs10757278), previously strongly associated with myocardial infarction, are independently associated with stroke and coronary events in patients with hypertension. METHODS: The Nordic Diltiazem study compared the effects of calcium antagonist and beta-blocker or diuretic-based antihypertensive treatment on cardiovascular events in 10 881 patients with hypertension, of whom 5262 patients provided DNA for the present study. We related SNPs rs2383207 and rs10757278 to stroke and to myocardial infarction and coronary revascularizations (coronary events) using crude and multivariate adjusted Cox proportional hazards models. RESULTS: The G-allele of both SNPs predicted coronary events in crude recessive models [hazard ratios = 1.36, 95% confidence interval (CI) = 1.04-1.79, P = 0.02 for rs10757278 and hazard ratios = 1.40, 95% CI = 1.08-1.81, P = 0.01 for rs2383207] as well as after adjustment for classical cardiovascular risk factors. The G-allele of both SNPs predicted incident stroke in crude additive models [rs2383207 hazard ratios = 1.25 (95% CI = 1.02-1.53), P = 0.04 and rs10757278 hazard ratios = 1.34 (95% CI = 1.09-1.65), P = 0.006], as well as after adjustment for classical cardiovascular risk factors and after additional adjustment for prevalent and incident coronary events, atrial fibrillation, ischemic heart disease and congestive heart failure. As was the case for coronary events, the excess genetic risk of stroke was driven by subjects homozygous for the risk allele. CONCLUSION: Genetic variation at the CDKN2A/CDKN2B locus predicts stroke in hypertensive patients. The genetic association with stroke is independent of classical cardiovascular risk factors and of all prevalent and incident coronary events, suggesting that gene variation at this locus promotes either atherosclerosis or another disease mechanism that is common to both coronary and cerebrovascular disease.},
  author       = {Wahlstrand, Björn and Orho-Melander, Marju and Delling, Lotta and Kjeldsen, Sverre and Narkiewicz, Krzysztof and Almgren, Peter and Hedner, Thomas and Melander, Olle},
  issn         = {1473-5598},
  language     = {eng},
  number       = {4},
  pages        = {769--773},
  publisher    = {ARRAY(0xa9c4d20)},
  series       = {Journal of Hypertension},
  title        = {The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension.},
  url          = {http://dx.doi.org/10.1097/HJH.0b013e328326f7eb},
  volume       = {27},
  year         = {2009},
}