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. 2019 Jan 24;18(1):25.
doi: 10.1186/s12944-019-0968-9.

Genetic variation in the leukotriene pathway is associated with myocardial infarction in the Chinese population

Yilan Li  1   2 , Xueming Xu  1   2 , Dandan Zhang  1   2 , Wei Cheng  1 , Yanan Zhang  3 , Bo Yu  1   2 , Yao Zhang  4   5
Affiliations

Genetic variation in the leukotriene pathway is associated with myocardial infarction in the Chinese population

Yilan Li et al. Lipids Health Dis. .

Abstract

Background: Genetic variation in the genes ALOX5 (arachidonate 5-lipoxygenase), ALOX5AP (arachidonate 5-lipoxygenase-activating protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to contribute to the risk of MI (myocardial infarction) in Caucasian and African American populations. All genes encode proteins playing a role in the synthesis of the pro-inflammatory leukotriene B mediators, possibly providing a link between MI and inflammation. The aim of the present study was to investigate whether these associations could be confirmed in the study of China MI patients. The study included 401 Han Chinese MI patients and 409 controls. Six tag single nucleotide polymorphisms (SNPs)-ALOX5 rs12762303 and rs12264801, ALOX5AP rs10507391, LTA4H rs2072512, rs2540487 and rs2540477-were selected. SNP genotyping was performed by an improved multiplex ligation detection reaction assay.

Results: The rs2540487 genotype was associated with the risk of MI in overdominant model (P = 0.008). rs12762303 and rs10507391 SNPs were significantly associated with lipid levels in MI patients (P < 0.006-0.008). Several SNPs interacted with alcohol consumption, cigarette smoking, and hypertension to modify TC, TG, LDL-C and CRE levels, and the risk of MI (P < 0.0017 for all). No association between the SNPs of LT pathway and susceptibility to MI was found (P > 0.05 for all).

Conclusions: Taken together, this study provides additional evidence that functional genetic variation of the LT pathway can mediate atherogenic processes and the risk of MI in Chinese.

Keywords: Arachidonate 5-lipoxygenase; Arachidonate 5-lipoxygenase-activating protein; Coronary artery disease; Myocardial infarction; Single nucleotide polymorphism.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University and all experimental procedures (DNA extraction and genotyping) complied with the Declaration of Helsinki (2003). All participates gave written informed consent to take part in the present study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The activation of 5-lipoxygenase (5-LO) pathway of AA metabolism by the enzymes 5-lipoxygenase activating protein (FLAP) and 5-lipoxygenase (5-LO) will catalyze the conversion of AA into the chemokine, leukotriene A4 (LTA4), which will be converted into other leukotrienes by the enzymes LTA4 hydrolase (LTA4H) and LTC4 synthase (LTC4S). These leukotrienes act on leukotriene receptors in lymphocytes, endothelial, and smooth muscle cells, which further enhance inflammatory reactions and subsequently, atherogenesis
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