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Association of ALOX5AP with ischemic stroke: a population-based case-control study
Ritesh Kaushal1, Prodipto Pal, Kathleen Alwell
1Department of Environmental Health, Center for Genome Information, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0525, USA.
Human Genetics
|March 28, 2007
Summary
Variants of Arachidonate 5-lipoxygenase activating protein (ALOX5AP) are linked to ischemic stroke in white populations. This study found significant associations in whites but not in blacks, highlighting potential ethnic differences in stroke genetics.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
Background:
- Arachidonate 5-lipoxygenase activating protein (ALOX5AP) gene variants have been previously linked to ischemic stroke and myocardial infarction.
- Replication studies have yielded conflicting results, and limited data exists for Black populations.
Purpose of the Study:
- To investigate the association between ALOX5AP single nucleotide polymorphisms (SNPs) and ischemic stroke in a prospective cohort of white and Black individuals.
- To address inconsistencies in previous findings and expand genetic association studies to underrepresented populations.
Main Methods:
- Prospective recruitment of ischemic stroke cases and population-based controls across 16 hospitals.
- Genotyping of selected SNPs (rs9579646, rs4769874) using HAPLOVIEW for allelic, genotypic, and haplotypic association testing.
- Logistic regression analysis adjusted for traditional cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking).
Main Results:
- Significant allelic and genotypic association of ALOX5AP SNPs (rs9579646, rs4769874) with ischemic stroke was observed in white individuals (P=0.019 and P<10(-4), respectively) after multiple testing correction.
- Haplotype analysis revealed significant associations with ischemic stroke and its subtypes in whites.
- While an overall haplotype association was noted in Black individuals, no significant associations were found for individual haplotypes, alleles, or genotypes, with marked differences in allele frequencies between ethnic groups.
Conclusions:
- Specific ALOX5AP variants are significantly associated with ischemic stroke and its subtypes in white populations.
- No significant association between the studied ALOX5AP variants and ischemic stroke was found in Black individuals, suggesting ethnic-specific genetic influences on stroke risk.
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