Candidate gene polymorphisms for ischemic stroke.
Ischemic stroke (IS) is a multifactorial disorder with strong evidence from twin, family, and animal model studies suggesting a genetic influence on risk and prognosis. Several candidate genes for IS have been proposed, but few have been replicated. We investigated the contribution of 67 candidate genes (369 single nucleotide polymorphisms [SNPs]) on the risk of IS in a North American population of European descent.



Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects.



None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing.



These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes.
Matarin
Mar
M
Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Brown
W Mark
WM
Dena
Hernandez
H
Britton
Angela
A
De Vrieze
Fabienne Wavrant
FW
Brott
Thomas G
TG
Brown
Robert D
RD
Worrall
Bradford B
BB
Case
L Douglas
LD
Chanock
Stephen J
SJ
Metter
E Jeffrey
EJ
Ferrucci
Luigi
L
Gamble
Dale
D
Hardy
John A
JA
Rich
Stephen S
SS
Singleton
Andrew
A
Meschia
James F
JF
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
D005819:Genetic Markers