Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction  

Oleh:

Allayee, Hooman ; Baylin, Ana ; Hartiala, Jaana ; Wijesuriya, Hemani ; Mehrabian, Margarete

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 88 no. 04 (Oct. 2008), page 934.

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2008.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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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