Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case-Cohort
Anders Gammelmark1,2, Michael S Nielsen1, Søren Lundbye-Christensen3
1Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
Background:
The 5-lipoxygenase pathway (5-LOX) has been implicated in the development of cardiovascular disease and studies have suggested that genetic polymorphisms related to key enzymes in this pathway may confer risk of myocardial infarction (MI). This study investigated the association of pre-selected genetic polymorphisms in four candidate genes of 5-LOX (arachidonate 5-lipoxygenase and its activating protein (ALOX-5 and FLAP), leukotriene A4 hydroxylase (LTA4-H) and leukotriene C4 synthase (LTC4-S)) with incident MI.
Methods:
In a Danish cohort including 57,053 participants, aged 50-64 at enrolment and recruited from 1993-97, we conducted a case-cohort study including cases with incident MI and a randomly selected sub cohort of 3,000 participants. Cases were identified from national registries through July 2013. A total of 22 SNPs were selected and genotyped using the commercially available KASP™ assay. A tandem-repeat polymorphism, located in the ALOX-5 gene, was genotyped by multi-titre plate sequencing. Haplotypes were inferred using PHASE 2.1.
Results:
During a median follow-up of 17.0 years we identified 3,089 cases of incident MI. In FLAP, two SNPs were negatively associated with incident MI (rs9551963 & rs17222842) while one SNP (rs2247570) located in LTA4-H, was associated with higher risk of MI when comparing subjects with two copies of the variant allele to homozygotes for the wild type. However, only rs17222842 remained significantly associated with MI after correcting for multiple testing. Furthermore, the promoter polymorphism rs59439148 was associated with risk of MI in men. For male carriers of two variant alleles we found a hazard ratio of 1.63 (95% CI: 1.06;2.52) compared to homozygotes for the wild type. Previously described haplotypes (Hap-A -B, -E and -K) were not associated with MI in our population.
Conclusion:
In conclusion, some common polymorphisms in the 5-lipoxygenase pathway were modestly associated with incident MI, suggesting a potential role for this pathway in the development of cardiovascular disease.
More Related Videos
08:51Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:26Coronary Artery Disease II: Pathophysiology
01:30Coronary Artery Disease I: Introduction
01:31Lipid-derived Compounds in the Human Body
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:29Pharmacogenomics: Identification of New Drug Targets