Document Detail


Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction.
MedLine Citation:
PMID:  18842779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 5-Lipoxygenase (5-LO) catalyzes the rate-limiting step of the biosynthesis of proinflammatory leukotrienes from arachidonic acid (AA) and has been associated with atherosclerosis in animal models and humans. We previously reported that variants of a 5-LO promoter repeat polymorphism were associated with carotid atherosclerosis in humans, an effect that was exacerbated by high dietary AA but mitigated by high dietary n-3 fatty acids.
OBJECTIVE: We sought to confirm these initial observations with a more clinically relevant phenotype such as myocardial infarction (MI).
DESIGN: The 5-LO polymorphism was genotyped in 1885 Costa Rican case-control pairs and tested for association with MI. Functional experiments were carried out to determine whether the associated alleles had differences in mRNA expression.
RESULTS: The frequency of variant genotype groups did not differ significantly between cases and controls. However, a significant gene x diet interaction was observed, in which, relative to the common 5 repeat allele, the 3 and 4 alleles were associated with a higher MI risk in the high (> or = 0.25 g/d) dietary AA group (odds ratio: 1.31; 95% CI: 1.07, 1.61) and with a lower risk in the low (<0. 25 g/d) AA group (0.77; 0.63, 0.94) (P for interaction = 0.015). Using allele-specific quantitation, the short alleles had expression approximately twice that of the 5 allele (P < 0.0001).
CONCLUSIONS: The 3 and 4 variants lead to higher 5-LO expression and provide additional evidence that these alleles are associated with greater risks of atherosclerosis and MI in the context of a high-AA diet.
Authors:
Hooman Allayee; Ana Baylin; Jaana Hartiala; Hemani Wijesuriya; Margarete Mehrabian; Aldons J Lusis; Hannia Campos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  88     ISSN:  1938-3207     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-09     Completed Date:  2008-11-04     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  934-40     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Arachidonate 5-Lipoxygenase / genetics*
Arachidonic Acid / administration & dosage*,  metabolism
Atherosclerosis / epidemiology,  genetics
Case-Control Studies
Confidence Intervals
Diet
Female
Gene Expression Regulation, Enzymologic
Gene Frequency
Genotype
Humans
Male
Middle Aged
Myocardial Infarction / enzymology,  epidemiology*,  genetics*
Nutrigenomics*
Odds Ratio
Polymorphism, Genetic*
RNA, Messenger / analysis,  metabolism
Risk Factors
Grant Support
ID/Acronym/Agency:
C06 RR10600-01/RR/NCRR NIH HHS; CA62528-01/CA/NCI NIH HHS; HL060692/HL/NHLBI NIH HHS; HL079353/HL/NHLBI NIH HHS; HL30568/HL/NHLBI NIH HHS; P01 HL028481/HL/NHLBI NIH HHS; P01 HL028481-20/HL/NHLBI NIH HHS; P01 HL030568/HL/NHLBI NIH HHS; P01 HL030568-190011/HL/NHLBI NIH HHS; RR14514-01/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 27YG812J1I/Arachidonic Acid; EC 1.13.11.34/Arachidonate 5-Lipoxygenase
Comments/Corrections

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