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

Nat Genet. 2006 Jan;38(1):68-74. doi: 10.1038/ng1692. Epub 2005 Nov 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics*
  • African Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Epoxide Hydrolases / genetics*
  • Epoxide Hydrolases / metabolism
  • European Continental Ancestry Group / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Haplotypes / genetics
  • Humans
  • Iceland
  • Linkage Disequilibrium
  • Molecular Sequence Data
  • Myocardial Infarction / genetics*

Substances

  • Epoxide Hydrolases
  • leukotriene A4 hydrolase

Associated data

  • RefSeq/NM_000895