Document Detail


Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status.
MedLine Citation:
PMID:  16675738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States. METHODS: The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.4 years of follow-up were compared with 560 controls. RESULTS: Marginal associations with stroke (P<0.10) were found for 3 polymorphisms. Stratification of the population by hypertension markedly strengthened the association. SNPs 9 (hazard ratio [HR], 0.48; 95% CI, 0.26 to 0.91), 42 (HR, 1.73; 95% CI, 1.10 to 2.70), 219 (HR, 1.73; 95% CI, 1.13 to 2.64), and 220 (HR, 1.56; 95% CI, 1.05 to 2.32) showed significant association with stroke (P<0.05) under a dominant model in subjects without hypertension at baseline, and SNP 175 was significantly associated with stroke under an additive model (HR, 0.76; 95% CI, 0.59 to 0.98) in subjects with hypertension. Furthermore, the microsatellite AC008818-1 showed association with stroke only in the nonhypertensive subjects. Based on results in Iceland, specific haplotypes were tested in SOF, and stratification by hypertension also affected these association results. CONCLUSIONS: These data are consistent with an association of the PDE4D gene with stroke in a non-Icelandic sample and suggest an effect of hypertension status.
Authors:
Victoria H Brophy; Sunhee K Ro; Brian K Rhees; Li-Yung Lui; Jocelyn M Lee; Nanette Umblas; L Gordon Bentley; Jia Li; Suzanne Cheng; Warren S Browner; Henry A Erlich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-04
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  37     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-29     Completed Date:  2006-06-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1385-90     Citation Subset:  IM    
Affiliation:
Roche Molecular Systems, Alameda, CA 94501, USA. victoria_h.brophy@roche.com
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MeSH Terms
Descriptor/Qualifier:
3',5'-Cyclic-AMP Phosphodiesterases / genetics*
Aged
Alleles
Brain Ischemia / complications*
Case-Control Studies
Cyclic Nucleotide Phosphodiesterases, Type 3
Cyclic Nucleotide Phosphodiesterases, Type 4
Female
Haplotypes
Humans
Hypertension / complications*
Iceland / ethnology
Microsatellite Repeats
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Stroke / etiology*,  genetics*
United States
Grant Support
ID/Acronym/Agency:
AG05394/AG/NIA NIH HHS; AG05407/AG/NIA NIH HHS; AR35582/AR/NIAMS NIH HHS; AR35583/AR/NIAMS NIH HHS; AR35584/AR/NIAMS NIH HHS; NS36016/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 3; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 4; EC 3.1.4.17/PDE4D protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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