Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population

A. Helgadottir, S. Gretasdottir, David Malcolm St Clair, A. Maolescu, John Kwok Shing Cheung, G. Thorleifsson, Alireza Pasdar, S. F. Grant, Lawrence Jeffrey Whalley, H. Hakonarson, U. Thorsteinsdottir, A. Kong, J. R. Gulcher, K. Stefansson, Mary Joan MacLeod

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)505-509
Number of pages4
JournalAmerican Journal of Human Genetics
Volume76
Issue number3
DOIs
Publication statusPublished - Mar 2005

Keywords

  • C-REACTIVE PROTEIN
  • ISCHEMIC-STROKE
  • CHILDHOOD INTELLIGENCE
  • GAELIC ANCESTRY
  • CONFERS RISK
  • ATHEROSCLEROSIS
  • INFLAMMATION
  • IDENTIFICATION
  • HOMOCYSTEINE
  • DISEASE

Cite this

Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. / Helgadottir, A.; Gretasdottir, S.; St Clair, David Malcolm; Maolescu, A.; Cheung, John Kwok Shing; Thorleifsson, G.; Pasdar, Alireza; Grant, S. F.; Whalley, Lawrence Jeffrey; Hakonarson, H.; Thorsteinsdottir, U.; Kong, A.; Gulcher, J. R.; Stefansson, K.; MacLeod, Mary Joan.

In: American Journal of Human Genetics, Vol. 76, No. 3, 03.2005, p. 505-509.

Research output: Contribution to journalArticle

Helgadottir, A, Gretasdottir, S, St Clair, DM, Maolescu, A, Cheung, JKS, Thorleifsson, G, Pasdar, A, Grant, SF, Whalley, LJ, Hakonarson, H, Thorsteinsdottir, U, Kong, A, Gulcher, JR, Stefansson, K & MacLeod, MJ 2005, 'Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population', American Journal of Human Genetics, vol. 76, no. 3, pp. 505-509. https://doi.org/10.1086/428066
Helgadottir, A. ; Gretasdottir, S. ; St Clair, David Malcolm ; Maolescu, A. ; Cheung, John Kwok Shing ; Thorleifsson, G. ; Pasdar, Alireza ; Grant, S. F. ; Whalley, Lawrence Jeffrey ; Hakonarson, H. ; Thorsteinsdottir, U. ; Kong, A. ; Gulcher, J. R. ; Stefansson, K. ; MacLeod, Mary Joan. / Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. In: American Journal of Human Genetics. 2005 ; Vol. 76, No. 3. pp. 505-509.
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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.",
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T1 - Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population

AU - Helgadottir, A.

AU - Gretasdottir, S.

AU - St Clair, David Malcolm

AU - Maolescu, A.

AU - Cheung, John Kwok Shing

AU - Thorleifsson, G.

AU - Pasdar, Alireza

AU - Grant, S. F.

AU - Whalley, Lawrence Jeffrey

AU - Hakonarson, H.

AU - Thorsteinsdottir, U.

AU - Kong, A.

AU - Gulcher, J. R.

AU - Stefansson, K.

AU - MacLeod, Mary Joan

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.

KW - C-REACTIVE PROTEIN

KW - ISCHEMIC-STROKE

KW - CHILDHOOD INTELLIGENCE

KW - GAELIC ANCESTRY

KW - CONFERS RISK

KW - ATHEROSCLEROSIS

KW - INFLAMMATION

KW - IDENTIFICATION

KW - HOMOCYSTEINE

KW - DISEASE

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DO - 10.1086/428066

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SP - 505

EP - 509

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

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ER -