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Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish
A Helgadottir1, S Gretarsdottir, D St Clair
1deCODE Genetics, Reykjavik, Iceland.
Insights
The 5-lipoxygenase-activating protein (ALOX5AP) gene variant HapA is associated with increased risk of stroke in Scotland, supporting its role in cardiovascular diseases. This finding replicates previous observations in Iceland and England.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Epidemiology
Background:
- Cardiovascular diseases like myocardial infarction (MI) and stroke are often linked to atherosclerosis.
- Multiple genetic and environmental factors contribute to atherosclerosis.
- Previous studies identified ALOX5AP variants (HapA and HapB) associated with MI and stroke in Icelandic and English populations.
Purpose of the Study:
- To investigate the association of ALOX5AP variants (HapA and HapB) with cardiovascular diseases in a Scottish population.
- To determine if the previously identified genetic risk factors for MI and stroke extend beyond Iceland.
Main Methods:
- Genotyping of seven single-nucleotide polymorphisms defining HapA and HapB.
- Case-control study involving 450 ischemic stroke patients and 710 controls from Scotland.
- Statistical analysis to assess haplotype frequencies and relative risk.
Main Results:
- The Icelandic at-risk haplotype HapA was significantly more frequent in Scottish stroke patients (33.4%) than in controls (26.4%), yielding a relative risk of 1.36 (P=.007).
- No significant association was found between HapB and ischemic stroke in the Scottish cohort.
- HapB showed overrepresentation in male stroke patients.
Conclusions:
- The association of the ALOX5AP HapA variant with stroke is replicated in a Scottish population, reinforcing its role in cardiovascular disease etiology.
- ALOX5AP variants may represent a significant genetic risk factor for stroke across different populations.
- Further research into ALOX5AP's role in cardiovascular diseases, particularly its sex-specific effects, is warranted.
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.
