TY - JOUR
T1 - Polymorphisms in migraine-associated gene, atp1a2, and ischemic stroke risk in a biracial population
T2 - The genetics of early onset stroke study
AU - Harriott, Andrea M.
AU - Dueker, Nicole
AU - Cheng, Yu Ching
AU - Ryan, Kathleen A.
AU - O'Connell, Jeffrey R.
AU - Stine, O. Colin
AU - McArdle, Patrick F.
AU - Wozniak, Marcella A.
AU - Stern, Barney J.
AU - Mitchell, Braxton D.
AU - Kittner, Steven J.
AU - Cole, John W.
N1 - Funding Information:
This work 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 Department of Veterans Affairs, Baltimore, Geriatrics Research, Education, and Clinical Center of Excellence; the American Heart Association Grant-in-Aid Program; the National Institute of Neurological Disorders and Stroke (NINDS) (Grants U01 NS069208-01 and R01 NS39987); the NIH Office of Research on Women’s Health (ORWH) (Grant R01 NS45012); the National Human Genome Research Institute (NHGRI) (Grant U01 HG004436). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.
PY - 2013
Y1 - 2013
N2 - In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain injury in animal models. To further explore these observations, we assessed the association between ATP1A2 polymorphisms, migraine, and the risk of ischemic stroke in participants of the Genetics of Early-Onset Stroke Study, a population-based case-control study of ischemic stroke among men and women aged 15-49. Using responses to a headache symptoms questionnaire, subjects were classified as having no migraine, or migraine with or without visual aura. Evaluating a total of 134 ATP1A2 polymorphisms genotyped using a combination of Illumina platforms (Cardiovascular Gene-centric 50 K SNP Array and HumanOmni1-Quad_v1-0_B Bead Chip), only one polymorphism (rs2070704) demonstrated a nominally significant association with stroke in an age-, gender-, ethnicity-adjusted model (OR = 0.83, 95% CI = 0.71-0.98, p = 0.025) and in a vascular risk factor model adjusting for age, gender, ethnicity, hypertension, diabetes, smoking, and myocardial infarction (OR = 0.74, 95% CI = 0.63-0.89, p = 0.001). Ethnicity-stratified analyses demonstrated a significant association for rs2070704 among African-Americans (OR = 0.68, 95% CI = 0.53-0.90, p = 0.005) but not Caucasians (OR = 0.82, 95% CI = 0.64-1.04, p = 0.107). These associations were unchanged when migraine subtypes were included as co-variates. We did not observe an association between ATP1A2 polymorphisms and migraine. While our results do not demonstrate a strong relationship between ATP1A2 polymorphisms and migraine associated stroke risk, the results are hypothesis generating and indicate that an association between ATP1A2 polymorphisms and stroke risk may exist. Additional studies are required.
AB - In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain injury in animal models. To further explore these observations, we assessed the association between ATP1A2 polymorphisms, migraine, and the risk of ischemic stroke in participants of the Genetics of Early-Onset Stroke Study, a population-based case-control study of ischemic stroke among men and women aged 15-49. Using responses to a headache symptoms questionnaire, subjects were classified as having no migraine, or migraine with or without visual aura. Evaluating a total of 134 ATP1A2 polymorphisms genotyped using a combination of Illumina platforms (Cardiovascular Gene-centric 50 K SNP Array and HumanOmni1-Quad_v1-0_B Bead Chip), only one polymorphism (rs2070704) demonstrated a nominally significant association with stroke in an age-, gender-, ethnicity-adjusted model (OR = 0.83, 95% CI = 0.71-0.98, p = 0.025) and in a vascular risk factor model adjusting for age, gender, ethnicity, hypertension, diabetes, smoking, and myocardial infarction (OR = 0.74, 95% CI = 0.63-0.89, p = 0.001). Ethnicity-stratified analyses demonstrated a significant association for rs2070704 among African-Americans (OR = 0.68, 95% CI = 0.53-0.90, p = 0.005) but not Caucasians (OR = 0.82, 95% CI = 0.64-1.04, p = 0.107). These associations were unchanged when migraine subtypes were included as co-variates. We did not observe an association between ATP1A2 polymorphisms and migraine. While our results do not demonstrate a strong relationship between ATP1A2 polymorphisms and migraine associated stroke risk, the results are hypothesis generating and indicate that an association between ATP1A2 polymorphisms and stroke risk may exist. Additional studies are required.
KW - ATP1A2
KW - Genetics
KW - Headache
KW - Migraine
KW - Stroke
KW - Young
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U2 - 10.1186/2193-1801-2-46
DO - 10.1186/2193-1801-2-46
M3 - Article
C2 - 23459313
AN - SCOPUS:84876521489
SN - 2193-1801
VL - 2
SP - 1
EP - 8
JO - SpringerPlus
JF - SpringerPlus
IS - 1
M1 - 46
ER -