TY - JOUR
T1 - Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population
T2 - The stroke prevention in young women study
AU - Cole, John W.
AU - Brown, David W.
AU - Giles, Wayne H.
AU - Stine, Oscar C.
AU - O'Connell, Jeffrey R.
AU - Mitchell, Braxton D.
AU - Sorkin, John D.
AU - Wozniak, Marcella A.
AU - Stern, Barney J.
AU - Sparks, Mary J.
AU - Dobbins, Mark T.
AU - Shoffner, Latasha T.
AU - Zappala, Nancy K.
AU - Reinhart, Laurie J.
AU - Kittner, Steven J.
N1 - Funding Information:
Funding acknowledgments: Dr. Cole was supported in part by the Department of Veterans Affairs, Baltimore, Office of Research and Development, Medical Research Service; the Department of Veterans Affairs Stroke Research Enhancement Award Program; the University of Maryland General Clinical Research Center (Grant M01 RR 165001), General Clinical Research Centers Program, National Center for Research Resources, NIH, and; an American Heart Association Beginning Grant-in-Aid (Grant 0665352U). Dr. Kittner was supported in part by the Department of Veterans Affairs, Baltimore, Office of Research and Development, Medical Research Service, and Geriatrics Research, Education and Clinical Center, and Stroke Research Enhancement Award Program; a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention; the National Institute of Neurological Disorders and Stroke and the NIH Office of Research on Women's Health; the National Institute on Aging Pepper Center (Grant P60 12583); and the University of Maryland General Clinical Research Center (Grant M01 RR 165001), General Clinical Research Centers Program, National Center for Research Resources, NIH. Dr. Sorkin was supported by the Baltimore VA Medical Center Geriatrics Research, Education, and Clinical Center; the University of Maryland Claude D. Pepper Older Americans Independence Center; the Clinical Nutrition Research Unit of the University of Maryland, and; the Baltimore VA Medical Center, Center for Excellence in Robotics.
PY - 2008/8/26
Y1 - 2008/8/26
N2 - Background: Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status. Methods: A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. Results: Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0-5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0-6.5, p = 0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11-.082, p = 0.02), but not among smokers (OR = 1.63, 95% CI = 0.48-5.58, p = 0.43); genotype by smoking interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09-3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62-1.39, p = 0.72); genotype by smoking interaction (p = 0.039). Conclusion: This study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.
AB - Background: Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status. Methods: A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. Results: Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0-5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0-6.5, p = 0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11-.082, p = 0.02), but not among smokers (OR = 1.63, 95% CI = 0.48-5.58, p = 0.43); genotype by smoking interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09-3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62-1.39, p = 0.72); genotype by smoking interaction (p = 0.039). Conclusion: This study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.
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U2 - 10.1186/1477-9560-6-11
DO - 10.1186/1477-9560-6-11
M3 - Article
C2 - 18727828
AN - SCOPUS:51649092150
SN - 1477-9560
VL - 6
JO - Thrombosis Journal
JF - Thrombosis Journal
M1 - 11
ER -