Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: A twin study

• Type of Material: Article
• Authors: Jinying Zhao, Tulane University; Jack Goldberg, University of Washington; Viola Vaccarino, Emory University
• Language: English
• Date: 2013-01-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ireland Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2012.10.048
• Title of Journal or Parent Work: Atherosclerosis
• ISSN: 0021-9150
• Volume: 226
• Issue: 1
• Start Page: 238
• End Page: 244
• Grant/Funding Information: The United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry.; This study was supported by grants 0730100N from the American Heart Association; and NIH grants K01AG034259, R01DK091369, R21HL092363-01A2, R01 HL68630, R01AG026255, and K24HL077506.
• Keywords: Gene x diet interaction; Life Sciences & Biomedicine; CARDIOVASCULAR-DISEASE; Science & Technology; Twin study; ASSOCIATION; Cardiovascular System & Cardiology; ISCHEMIC-STROKE; INTIMA-MEDIA THICKNESS; PHYSICAL-ACTIVITY; ALOX5AP GENE; ARACHIDONATE 5-LIPOXYGENASE-ACTIVATING PROTEIN; Peripheral Vascular Disease; Cardiac & Cardiovascular Systems; FATTY-ACIDS; MYOCARDIAL-INFARCTION; Leukotriene haplotype; Carotid atherosclerosis; ACTIVATING PROTEIN
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

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 PHapE×n-3 = 0.03, PHapE×n-6 = 0.015). Conclusion: 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.