A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.

2.50
Hdl Handle:
http://hdl.handle.net/2336/15739
Title:
A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
Authors:
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
Citation:
Nat. Genet. 2006, 38(1):68-74
Issue Date:
1-Jan-2006
Abstract:
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/ng1692

Full metadata record

DC FieldValue Language
dc.contributor.authorHelgadottir, Anna-
dc.contributor.authorManolescu, Andrei-
dc.contributor.authorHelgason, Agnar-
dc.contributor.authorThorleifsson, Gudmar-
dc.contributor.authorThorsteinsdottir, Unnur-
dc.contributor.authorGudbjartsson, Daniel F-
dc.contributor.authorGretarsdottir, Solveig-
dc.contributor.authorMagnusson, Kristinn P-
dc.contributor.authorGudmundsson, Gudmundur-
dc.contributor.authorHicks, Andrew-
dc.contributor.authorJonsson, Thorlakur-
dc.contributor.authorGrant, Struan F A-
dc.contributor.authorSainz, Jesus-
dc.contributor.authorO'Brien, Stephen J-
dc.contributor.authorSveinbjornsdottir, Sigurlaug-
dc.contributor.authorValdimarsson, Einar M-
dc.contributor.authorMatthiasson, Stefan E-
dc.contributor.authorLevey, Allan I-
dc.contributor.authorAbramson, Jerome L-
dc.contributor.authorReilly, Murdach P-
dc.contributor.authorVaccarino, Viola-
dc.contributor.authorWolfe, Megan L-
dc.contributor.authorGudnason, Vilmundur-
dc.contributor.authorQuyyumi, Arshed A-
dc.contributor.authorTopol, Eric J-
dc.contributor.authorRader, Daniel J-
dc.contributor.authorThorgeirsson, Gudmundur-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorHakonarson, Hakon-
dc.contributor.authorKong, Augustine-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2008-01-07T12:57:28Z-
dc.date.available2008-01-07T12:57:28Z-
dc.date.issued2006-01-01-
dc.date.submitted2007-01-07-
dc.identifier.citationNat. Genet. 2006, 38(1):68-74en
dc.identifier.issn1061-4036-
dc.identifier.pmid16282974-
dc.identifier.doi10.1038/ng1692-
dc.identifier.urihttp://hdl.handle.net/2336/15739-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractVariants 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.en
dc.language.isoenen
dc.publisherNature Pub. Co.,en
dc.relation.urlhttp://dx.doi.org/10.1038/ng1692en
dc.subject.meshAfrican Americansen
dc.subject.meshAfrican Continental Ancestry Groupen
dc.subject.meshCase-Control Studiesen
dc.subject.meshEpoxide Hydrolasesen
dc.subject.meshEuropean Continental Ancestry Groupen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHaplotypesen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshLinkage Disequilibriumen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMyocardial Infarctionen
dc.subject.meshVariation (Genetics)en
dc.titleA variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.en
dc.typeArticleen

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