TY - JOUR
T1 - Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population
AU - Helgadottir, A.
AU - Gretarsdottir, S.
AU - St. Clair, D.
AU - Manolescu, A.
AU - Cheung, J.
AU - Thorleifsson, G.
AU - Pasdar, A.
AU - Grant, S. F.A.
AU - Whalley, L. J.
AU - Hakonarson, H.
AU - Thorsteinsdottir, U.
AU - Kong, A.
AU - Gulcher, J.
AU - Stefansson, K.
AU - MacLeod, M. J.
N1 - Funding Information:
The authors thank Thorbjorg Jonsdottir and personnel at the deCODE core facilities for valuable contributions. The authors acknowledge the support of the Chief Scientist's Office, Scottish Executive.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=13844289142&partnerID=8YFLogxK
U2 - 10.1086/428066
DO - 10.1086/428066
M3 - Article
C2 - 15640973
AN - SCOPUS:13844289142
SN - 0002-9297
VL - 76
SP - 505
EP - 509
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -