title: Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: a twin study.
abstract: OBJECTIVE
  Atherosclerosis is an inflammatory process resulting from the interaction between genetic and environmental factors. Leukotrienes are inflammatory mediators generated from arachidonic acid, and genetic polymorphisms involved in leukotriene metabolism are implicated in atherosclerosis. The objectives of this study are to examine whether genetic variants in key leukotriene enzymes are associated with atherosclerosis, and whether dietary intake of competing leukotriene substrates modifies the effect of leukotriene variants on atherosclerosis.
  
  
  METHODS
  Atherosclerosis was assessed by common carotid intima-media thickness (IMT) using ultrasound. Sequence variants within arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms (SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The associations between genetic polymorphisms and carotid atherosclerosis, and gene × diet interactions were examined by generalized estimating equation controlling for potential confounders.
  
  
  RESULTS
  A six-SNP haplotype in LTA4H, designated HapE, was significantly associated with carotid IMT after adjusting for known coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins not carrying (695 μm vs. 750 μm, p = 0.0007). Moreover, dietary intake of polyunsaturated fatty acids strongly augmented the cardioprotective effect of HapE among those with this haplotype but not those without, suggesting a haplotype × diet interaction (interaction P(HapE×n-3) = 0.03, P(HapE×n-6) = 0.015).
  
  
  CONCLUSIONS
  We identified a novel leukotriene haplotype that appears to be protective toward subclinical atherosclerosis. This association is modified by dietary intake of polyunsaturated fatty acids.
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 2010-SL18, New Orleans, LA 70112, United States. jzhao5@tulane.edu
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.forename: Jack
authors.initials: J
authors.lastname: Goldberg
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
mesh_terms: D050197:Atherosclerosis / Q000235:genetics*; D004032:Diet; D004200:Diseases in Twins / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase