A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a...
Published in: | Nature Genetics |
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Online Access: | http://hdl.handle.net/2336/15739 https://doi.org/10.1038/ng1692 |
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/15739 2023-05-15T16:50:57+02:00 A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Helgadottir, Anna Manolescu, Andrei Helgason, Agnar Thorleifsson, Gudmar Thorsteinsdottir, Unnur Gudbjartsson, Daniel F Gretarsdottir, Solveig Magnusson, Kristinn P Gudmundsson, Gudmundur Hicks, Andrew Jonsson, Thorlakur Grant, Struan F A Sainz, Jesus O'Brien, Stephen J Sveinbjornsdottir, Sigurlaug Valdimarsson, Einar M Matthiasson, Stefan E Levey, Allan I Abramson, Jerome L Reilly, Murdach P Vaccarino, Viola Wolfe, Megan L Gudnason, Vilmundur Quyyumi, Arshed A Topol, Eric J Rader, Daniel J Thorgeirsson, Gudmundur Gulcher, Jeffrey R Hakonarson, Hakon Kong, Augustine Stefansson, Kari 2007-01-07 http://hdl.handle.net/2336/15739 https://doi.org/10.1038/ng1692 en eng Nature Pub. Co. http://dx.doi.org/10.1038/ng1692 Nat. Genet. 2006, 38(1):68-74 1061-4036 16282974 doi:10.1038/ng1692 http://hdl.handle.net/2336/15739 African Americans African Continental Ancestry Group Case-Control Studies Epoxide Hydrolases European Continental Ancestry Group Genetic Predisposition to Disease Haplotypes Humans Iceland Linkage Disequilibrium Molecular Sequence Data Myocardial Infarction Variation (Genetics) Article 2007 ftlandspitaliuni https://doi.org/10.1038/ng1692 2022-05-29T08:21:04Z To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive Nature Genetics 38 1 68 74 |
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Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
language |
English |
topic |
African Americans African Continental Ancestry Group Case-Control Studies Epoxide Hydrolases European Continental Ancestry Group Genetic Predisposition to Disease Haplotypes Humans Iceland Linkage Disequilibrium Molecular Sequence Data Myocardial Infarction Variation (Genetics) |
spellingShingle |
African Americans African Continental Ancestry Group Case-Control Studies Epoxide Hydrolases European Continental Ancestry Group Genetic Predisposition to Disease Haplotypes Humans Iceland Linkage Disequilibrium Molecular Sequence Data Myocardial Infarction Variation (Genetics) Helgadottir, Anna Manolescu, Andrei Helgason, Agnar Thorleifsson, Gudmar Thorsteinsdottir, Unnur Gudbjartsson, Daniel F Gretarsdottir, Solveig Magnusson, Kristinn P Gudmundsson, Gudmundur Hicks, Andrew Jonsson, Thorlakur Grant, Struan F A Sainz, Jesus O'Brien, Stephen J Sveinbjornsdottir, Sigurlaug Valdimarsson, Einar M Matthiasson, Stefan E Levey, Allan I Abramson, Jerome L Reilly, Murdach P Vaccarino, Viola Wolfe, Megan L Gudnason, Vilmundur Quyyumi, Arshed A Topol, Eric J Rader, Daniel J Thorgeirsson, Gudmundur Gulcher, Jeffrey R Hakonarson, Hakon Kong, Augustine Stefansson, Kari A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
topic_facet |
African Americans African Continental Ancestry Group Case-Control Studies Epoxide Hydrolases European Continental Ancestry Group Genetic Predisposition to Disease Haplotypes Humans Iceland Linkage Disequilibrium Molecular Sequence Data Myocardial Infarction Variation (Genetics) |
description |
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. |
format |
Article in Journal/Newspaper |
author |
Helgadottir, Anna Manolescu, Andrei Helgason, Agnar Thorleifsson, Gudmar Thorsteinsdottir, Unnur Gudbjartsson, Daniel F Gretarsdottir, Solveig Magnusson, Kristinn P Gudmundsson, Gudmundur Hicks, Andrew Jonsson, Thorlakur Grant, Struan F A Sainz, Jesus O'Brien, Stephen J Sveinbjornsdottir, Sigurlaug Valdimarsson, Einar M Matthiasson, Stefan E Levey, Allan I Abramson, Jerome L Reilly, Murdach P Vaccarino, Viola Wolfe, Megan L Gudnason, Vilmundur Quyyumi, Arshed A Topol, Eric J Rader, Daniel J Thorgeirsson, Gudmundur Gulcher, Jeffrey R Hakonarson, Hakon Kong, Augustine Stefansson, Kari |
author_facet |
Helgadottir, Anna Manolescu, Andrei Helgason, Agnar Thorleifsson, Gudmar Thorsteinsdottir, Unnur Gudbjartsson, Daniel F Gretarsdottir, Solveig Magnusson, Kristinn P Gudmundsson, Gudmundur Hicks, Andrew Jonsson, Thorlakur Grant, Struan F A Sainz, Jesus O'Brien, Stephen J Sveinbjornsdottir, Sigurlaug Valdimarsson, Einar M Matthiasson, Stefan E Levey, Allan I Abramson, Jerome L Reilly, Murdach P Vaccarino, Viola Wolfe, Megan L Gudnason, Vilmundur Quyyumi, Arshed A Topol, Eric J Rader, Daniel J Thorgeirsson, Gudmundur Gulcher, Jeffrey R Hakonarson, Hakon Kong, Augustine Stefansson, Kari |
author_sort |
Helgadottir, Anna |
title |
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
title_short |
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
title_full |
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
title_fullStr |
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
title_full_unstemmed |
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
title_sort |
variant of the gene encoding leukotriene a4 hydrolase confers ethnicity-specific risk of myocardial infarction. |
publisher |
Nature Pub. Co. |
publishDate |
2007 |
url |
http://hdl.handle.net/2336/15739 https://doi.org/10.1038/ng1692 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://dx.doi.org/10.1038/ng1692 Nat. Genet. 2006, 38(1):68-74 1061-4036 16282974 doi:10.1038/ng1692 http://hdl.handle.net/2336/15739 |
op_doi |
https://doi.org/10.1038/ng1692 |
container_title |
Nature Genetics |
container_volume |
38 |
container_issue |
1 |
container_start_page |
68 |
op_container_end_page |
74 |
_version_ |
1766041064981921792 |