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BACKGROUND AND PURPOSE:
The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated
with ischemic stroke in an Icelandic population. The association was found
predominately with large vessel and cardioembolic stroke. However, 2 recent
reports were unable to confirm this association, although a trend toward
association with cardioembolic stroke was reported. None of the reports
included significant proportions of blacks. We tested for genotype and
haplotype association of polymorphisms of the PDE4D gene with ischemic
stroke in a population-based, biracial, case-control study.
METHODS:
A total of 357 cases of ischemic stroke and 482 stroke-free controls from
the same community were examined. Single nucleotide polymorphisms (SNPs)
were chosen based on significant associations reported previously. Linkage
disequilibrium (LD), SNP, and haplotype association analysis was performed
using PHASE 2.0 and Haploview 3.2.
RESULTS:
Although several univariate associations were identified, only 1 SNP
(rs2910829) was found to be significantly associated with cardioembolic
stroke among both whites and blacks. The rs152312 SNP was associated with
cardioembolic stroke among whites after multiple comparison corrections. The
same SNP was not associated with cardioembolic stroke among blacks. However,
significant haplotype association was identified for both whites and blacks
for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin.
Haplotype association was identified for small vessel stroke among whites.
CONCLUSIONS:
PDE4D is a risk factor for ischemic stroke and, in particular, for
cardioembolic stroke, among whites and blacks. Further study of this gene is
warranted.
Reference:
Stroke. 2005
Dec 22 |