Trial reportPloS one2016
Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case-Cohort Study.
Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 19 citations in OpenAlex.
- Selected Genes Associated With CVD-Related Diseases, Pathways, and Nutrigenetics.Journal of lipid and atherosclerosis · 2026Review
- Cytokine and Oxylipin Production in Resting and LPS-Stimulated Monocytes From Americans of African Ancestry Are Influenced by ALOX5 Promoter Tandem Repeat Polymorphisms.Mediators of inflammation · 2026Article
- Genetic insights into 5-LOX-activating protein: a narrative review of disease associations.Human genomics · 2025Review
- Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.BMC medical genomics · 2024Article
- Relationship between Arachidonate 5-Lipoxygenase-Activating Protein Gene and Peripheral Arterial Disease in Elderly Patients Undergoing General Surgery: A Retrospective Observational Study.International journal of environmental research and public health · 2023Observational
- Genetic variation in the leukotriene pathway is associated with myocardial infarction in the Chinese population.Lipids in health and disease · 2019Article
- Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases.Mediators of inflammation · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsIn 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.
resultsDuring 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.
conclusionIn 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.
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