title: Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population.
abstract: Cardiovascular diseases, including myocardial infarction (MI) and stroke, most often occur on the background of atherosclerosis, a condition attributed to the interactions between multiple genetic and environmental risk factors. We recently reported a linkage and association study of MI and stroke that yielded a genetic variant, HapA, in the gene encoding 5-lipoxygenase-activating protein (ALOX5AP), that associates with both diseases in Iceland. We also described another ALOX5AP variant, HapB, that associates with MI in England. To further assess the contribution of the ALOX5AP variants to cardiovascular diseases in a population outside Iceland, we genotyped seven single-nucleotide polymorphisms that define both HapA and HapB from 450 patients with ischemic stroke and 710 controls from Aberdeenshire, Scotland. The Icelandic at-risk haplotype, HapA, had significantly greater frequency in Scottish patients than in controls. The carrier frequency in patients and controls was 33.4% and 26.4%, respectively, which resulted in a relative risk of 1.36, under the assumption of a multiplicative model (P=.007). We did not detect association between HapB and ischemic stroke in the Scottish cohort. However, we observed that HapB was overrepresented in male patients. This replication of haplotype association with stroke in a population outside Iceland further supports a role for ALOX5AP in cardiovascular diseases.
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: A
authors.initials: A
authors.lastname: Helgadottir
authors.forename: S
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: D
authors.initials: D
authors.lastname: St Clair
authors.forename: A
authors.initials: A
authors.lastname: Manolescu
authors.forename: J
authors.initials: J
authors.lastname: Cheung
authors.forename: G
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: A
authors.initials: A
authors.lastname: Pasdar
authors.forename: S F A
authors.initials: SF
authors.lastname: Grant
authors.forename: L J
authors.initials: LJ
authors.lastname: Whalley
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
authors.forename: U
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: A
authors.initials: A
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Gulcher
authors.forename: K
authors.initials: K
authors.lastname: Stefansson
authors.forename: M J
authors.initials: MJ
authors.lastname: MacLeod
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007055:Iceland; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012606:Scotland; D020521:Stroke / Q000235:genetics*
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins