Gene variants associated with ischemic stroke: the cardiovascular health study.
OBJECTIVE
The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.


METHODS
Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).


RESULTS
In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS.


CONCLUSIONS
The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.
Luke
May M
MM
Celera, Alameda, California 94502, USA. may.luke@celera.com
O'Meara
Ellen S
ES
Rowland
Charles M
CM
Shiffman
Dov
D
Bare
Lance A
LA
Arellano
Andre R
AR
Longstreth
W T
WT
Lumley
Thomas
T
Rice
Kenneth
K
Tracy
Russell P
RP
Devlin
James J
JJ
Psaty
Bruce M
BM
D000368:Aged; D000483:Alleles; D044383:Black People; D002545:Brain Ischemia / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People; D001741:Black or African American