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

  1. Author:
    Helgadottir, A.
    Manolescu, A.
    Helgason, A.
    Thorleifsson, G.
    Thorsteinsdottir, U.
    Gudbjartsson, D. F.
    Gretarsdottir, S.
    Magnusson, K. P.
    Gudmundsson, G.
    Hicks, A.
    Jonsson, T.
    Grant, S. F. A.
    Sainz, J.
    O'Brien, S. J.
    Sveinbjornsdottir, S.
    Valdimarsson, E. M.
    Matthiasson, S. E.
    Levey, A. I.
    Abramson, J. L.
    Reilly, M. P.
    Vaccarino, V.
    Wolfe, M. L.
    Gudnason, V.
    Quyyumi, A. A.
    Topol, E. J.
    Rader, D. J.
    Thorgeirsson, G.
    Gulcher, J. R.
    Hakonarson, H.
    Kong, A.
    Stefansson, K.

  2. Author Address

    deCODE Genet Inc, IS-101 Reykjavik, Iceland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Natl Univ Hosp Reykjavik, Reykjavik, Iceland. Emory Univ, Sch Med, Atlanta, GA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Iceland Heart Assoc, Reykjavik, Iceland. Cleveland Clin Fdn, Cleveland, OH 44195 USA.;Stefansson, K, deCODE Genet Inc, Sturlugata 8, IS-101 Reykjavik, Iceland.;kstefans@decode.is
    1. Year: 2006
    2. Date: Jan
  2. Journal: Nature Genetics
    1. 38
    2. 1
    3. Pages: 68-74
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. 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(1). 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.

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  2. DOI: 10.1038/ng1692
  3. View record in Web of Science®
  4. WOS: 000234227200019

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