期刊
AMERICAN JOURNAL OF CLINICAL NUTRITION
卷 88, 期 4, 页码 934-940出版社
AMER SOC CLINICAL NUTRITION
DOI: 10.1093/ajcn/88.4.934
关键词
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资金
- National Institutes of Health [HL079353, HL30568, HL060692]
- American Heart Association [0355031Y]
- National Center for Research Resources [C06 RR10600-01, C06 CA62528-01, C06 RR14514- 01]
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 (>= 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.
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