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

Yilan Li,Bo Yu,Xueming Xu,Yanan Zhang,Yao Zhang,Dandan Zhang,Wei Cheng

doi:10.1186/s12944-019-0968-9

Abstract

BackgroundGenetic 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.ResultsThe 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).ConclusionsTaken 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.

Highlights

Genetic variation in the genes Arachidonate 5-lipoxygenase (ALOX5), ALOX5 activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) has previously been shown to contribute to the risk of Myocardial infarction (MI) in Caucasian and African American populations
Our study showed that ALOX5 rs12762303 was associated with fasting blood glucose (FBG) levels but not with MI in Chinese population, which is consistent with the studies by Assimes et al [10]
Our study showed that ALOX5AP rs10507391 was associated with total cholesterol (TC) levels but we didn’t observe any association between rs10507391 and the risk of MI

Summary

Introduction

Genetic variation in the genes ALOX5 (arachidonate 5-lipoxygenase), ALOX5AP (arachidonate 5lipoxygenase-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. A necessary cofactor in this reaction is the 5-lipoxygenase-activating protein (FLAP), encoded by the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene, is an important mediator of the activity of 5-lipoxygenase, a key enzyme in the biosynthesis of leukotrienes [10]. The LTA4H gene encodes leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP [11]. LTA4 is further hydrolyzed by leukotriene A4 hydrolase (LTA4H) to leukotriene B4 (LTB4) or conjugated to produce a series of three related

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