Arachidonate 5-lipoxygenase (5-LO) promoter genotype and risk of myocardial infarction: a case-control study.
BACKGROUND
Leukotrienes are inflammatory mediators derived from arachidonic acid via the 5-lipoxygenase pathway. Both experimental and clinical studies implicate the 5-lipoxygenase pathway in the pathophysiology of atherosclerosis. In a previous study, a microsatellite polymorphism in the 5-lipoxygenase gene promoter involving the binding site for the transcription factor Sp1, was associated with carotid intima media thickness (CIMT). Compared to subjects carrying the common allele, subjects carrying two variant alleles had significantly greater CIMT. Elevated CIMT is a risk factor for coronary events. In this study we investigated whether carriage of two variants alleles for the 5-lipoxygenase promoter polymorphism is associated with increased risk of myocardial infarction (MI).


METHODS
1464 subjects, comprising 746 MI cases (under 65 years of age) and 718 controls, were genotyped for the 5-lipoxygenase microsatellite polymorphism by PCR amplification of the promoter region and allele discrimination by capillary electrophoresis.


RESULTS
The distribution of subjects grouped into those homozygote for the common allele, subjects carrying one variant allele, and subjects carrying two variant alleles was similar in cases and controls (cases: 66.9%/29.8%/3.3%, controls: 66.0%/29.4%/4.6%, p=0.48). The odds ratio for MI for subjects carrying two variant alleles compared to subjects carrying at least one common allele was 0.72 (95% CI: 0.42-1.22, p=0.22). The odds ratio was not affected by adjustment for other demographic risk factors.


CONCLUSIONS
Despite their association with a marker of atherosclerosis, variant 5-lipoxygenase promoter genotypes are not a major risk factor for MI, at least in Caucasian subjects of Northern European origin.
Maznyczka
Annette
A
Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
Braund
Peter
P
Mangino
Massimo
M
Samani
Nilesh J
NJ
D000328:Adult; D000483:Alleles; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000502:physiology; D001665:Binding Sites; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D016329:Sp1 Transcription Factor / Q000378:metabolism
D016329:Sp1 Transcription Factor; D001094:Arachidonate 5-Lipoxygenase