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Ischaemic stroke in hypertensive patients is associated with variations in the PDE4D genome region.

Lövkvist, Håkan LU ; Smith, Jan Gustav; Luthman, Holger LU ; Höglund, Peter LU ; Norrving, Bo LU ; Kristoffersson, Ulf LU ; Jönsson, Ann-Cathrin LU and Lindgren, Arne LU (2008) In European Journal of Human Genetics 16. p.1117-1125
Abstract
Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies reported ambiguous findings. We examined 932 ischaemic stroke patients from a Swedish population-based stroke register, and 396 control subjects. We assessed possible associations between ischaemic stroke and nine preselected SNPs in the chromosome regions of the PDE4D gene, including rs12188950 (SNP45) and rs3887175 (SNP39); the ALOX5AP gene, including rs17222814 (SG13S25) and the promoter region of the MHC class II transactivator, MHC2TA. The T allele of SNP45 showed negative association with ischaemic... (More)
Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies reported ambiguous findings. We examined 932 ischaemic stroke patients from a Swedish population-based stroke register, and 396 control subjects. We assessed possible associations between ischaemic stroke and nine preselected SNPs in the chromosome regions of the PDE4D gene, including rs12188950 (SNP45) and rs3887175 (SNP39); the ALOX5AP gene, including rs17222814 (SG13S25) and the promoter region of the MHC class II transactivator, MHC2TA. The T allele of SNP45 showed negative association with ischaemic stroke (odds ratio, OR=0.72; 95% confidence interval (CI): 0.58-0.91; P=0.0055). Among hypertensive subjects, this influence of the T allele of SNP45, and the T allele of SNP39, were more pronounced (with OR=0.52; 95% CI: 0.37-0.73; P=0.0001 and OR=0.57; 95% CI: 0.41-0.79; P=0.0007, respectively). These SNPs also interacted with hypertension with a relative excess risk due to interaction of -1.66 (P=0.0002) for SNP45 and -1.65 (P=0.0005) for SNP39. The P-values remained significant after correction for multiple testing. Among nonhypertensives, the A allele of SG13S25 indicated increased stroke risk (OR=1.82; 95% CI: 1.21-2.74; P=0.0039; not significant after Bonferroni correction). SNP45 was associated with ischaemic stroke even when controlling for hypertension, diabetes, heart disease and smoking. Our meta-analysis of 13 studies (including ours) showed no overall influence of SNP45 on ischaemic stroke. However, the 13 studies may differ because of nonrandom causes, as suggested by the heterogeneity test (P=0.042). This might support previously undetected mechanisms causing fluctuating ischaemic stroke risk.European Journal of Human Genetics advance online publication, 9 April 2008; doi:10.1038/ejhg.2008.62. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
European Journal of Human Genetics
volume
16
pages
1117 - 1125
publisher
Nature Publishing Group
external identifiers
  • wos:000258929800014
  • pmid:18398440
  • scopus:50149096173
ISSN
1476-5438
DOI
10.1038/ejhg.2008.62
language
English
LU publication?
yes
id
26ea258d-b7be-46bc-923e-df6b88aa1193 (old id 1147596)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18398440?dopt=Abstract
date added to LUP
2008-05-06 14:17:12
date last changed
2017-04-09 04:29:37
@article{26ea258d-b7be-46bc-923e-df6b88aa1193,
  abstract     = {Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies reported ambiguous findings. We examined 932 ischaemic stroke patients from a Swedish population-based stroke register, and 396 control subjects. We assessed possible associations between ischaemic stroke and nine preselected SNPs in the chromosome regions of the PDE4D gene, including rs12188950 (SNP45) and rs3887175 (SNP39); the ALOX5AP gene, including rs17222814 (SG13S25) and the promoter region of the MHC class II transactivator, MHC2TA. The T allele of SNP45 showed negative association with ischaemic stroke (odds ratio, OR=0.72; 95% confidence interval (CI): 0.58-0.91; P=0.0055). Among hypertensive subjects, this influence of the T allele of SNP45, and the T allele of SNP39, were more pronounced (with OR=0.52; 95% CI: 0.37-0.73; P=0.0001 and OR=0.57; 95% CI: 0.41-0.79; P=0.0007, respectively). These SNPs also interacted with hypertension with a relative excess risk due to interaction of -1.66 (P=0.0002) for SNP45 and -1.65 (P=0.0005) for SNP39. The P-values remained significant after correction for multiple testing. Among nonhypertensives, the A allele of SG13S25 indicated increased stroke risk (OR=1.82; 95% CI: 1.21-2.74; P=0.0039; not significant after Bonferroni correction). SNP45 was associated with ischaemic stroke even when controlling for hypertension, diabetes, heart disease and smoking. Our meta-analysis of 13 studies (including ours) showed no overall influence of SNP45 on ischaemic stroke. However, the 13 studies may differ because of nonrandom causes, as suggested by the heterogeneity test (P=0.042). This might support previously undetected mechanisms causing fluctuating ischaemic stroke risk.European Journal of Human Genetics advance online publication, 9 April 2008; doi:10.1038/ejhg.2008.62.},
  author       = {Lövkvist, Håkan and Smith, Jan Gustav and Luthman, Holger and Höglund, Peter and Norrving, Bo and Kristoffersson, Ulf and Jönsson, Ann-Cathrin and Lindgren, Arne},
  issn         = {1476-5438},
  language     = {eng},
  pages        = {1117--1125},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {Ischaemic stroke in hypertensive patients is associated with variations in the PDE4D genome region.},
  url          = {http://dx.doi.org/10.1038/ejhg.2008.62},
  volume       = {16},
  year         = {2008},
}