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

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??0.05 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.

SUBMITTER: Li Y

PROVIDER: S-EPMC6346589 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Li Yilan Y Xu Xueming X Zhang Dandan D Cheng Wei W Zhang Yanan Y Yu Bo B Zhang Yao Y

Lipids in health and disease 20190124 1

<h4>Background</h4>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 ...[more]

PMID: 30678701

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Project description:OBJECTIVE:Atherosclerosis plays a key role in the inducibility and persistence of coronary heart disease. Clinical evidence, in vitro and in vivo studies have implicated Urotensin II (U-II/UTS2) in the development of atherosclerosis and coronary artery disease, contributing to the (patho) physiological regulation of cardiovascular homeostasis in humans. Increased U-II plasma levels have been reported in patients with atherosclerosis and coronary heart disease. Considering these, our objective was to evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to coronary heart disease and myocardial infarction in a Chinese population. METHODS:A case-control study was designed to compare the distribution of alleles and genotypes between case group (subjects with myocardial infarction, n=409) and control group (subjects with coronary heart disease, n=830). The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. RESULTS:We did not identify statistically significant differences between the myocardial infarction and coronary heart disease groups, neither with regard to the frequency of genotype/variant at the Ser89Asn locus nor at the Thr21Met locus. When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in female subjects in both additive tested inheritance model (OR=0.257, 95% CI: 0.074-0.896, P=0.033) and recessive tested inheritance model (OR=0.280, 95% CI: 0.082-0.955, P=0.042). For subjects with myocardial infarction, we identified statistically significant differences between the ST-segment elevation myocardial infarction and non ST-segment elevation myocardial infarction groups. Differences in genotype distribution of polymorphism Ser89Asn not Thr21Met were seen in both additive tested inheritance model (OR=0.202, 95% CI: 0.049-0.833, P=0.027) and recessive tested inheritance model (OR=0.208, 95% CI: 0.052-0.835, P=0.027). When stratified by sex, differences in genotype distribution of polymorphism Ser89Asn were only seen in male subjects in both additive tested inheritance model (OR=0.208, 95% CI: 0.049-0.890, P=0.034) and recessive tested inheritance model (OR=0.197, 95% CI: 0.047-0.824, P=0.026). CONCLUSIONS:Ser89Asn (S89N) polymorphisms of the UTS2 gene were significantly associated with coronary heart disease and myocardial infarction in Chinese population. Additionally, we demonstrated that Genotype Asn89Asn may imply a potential benefit role for myocardial infarction.

Project description:Background and purposeAtherothrombotic cerebral infarction [atherothrombotic stroke (ATS)] shares common risk factors and pathophysiological mechanisms with coronary artery disease (CAD), and both diseases appear to have common susceptibility loci. The muscle RAS oncogene homolog gene (MRAS) has been identified as a susceptibility locus for CAD and is implicated in atherosclerosis. The aim of this study was to elucidate whether the single-nucleotide polymorphisms (SNPs) and haplotypes of MRAS are associated with increased risk of ATS in a population of Han Chinese.MethodsA case-controlled association study was conducted in which only patients with ATS (identified as a major subtype in the Korean modification of the Trial of Org 10172 in Acute Stroke Treatment classification) were enrolled. Subgroup analyses were carried out to determine whether the effect of the MRAS polymorphism was specific to age and gender among the subjects.ResultsIn total, 194 ATS and 186 control subjects were included in the present study. Two tagging SNPs were identified in MRAS (rs40593 and rs3755751). A multivariate regression analysis revealed a positive association between rs40593 and ATS under dominant and additive models after adjustment for covariates. Subgroup analyses revealed that there were no gender differences with respect to allele or genotype frequencies between the groups. The AG genotype for rs40593 (p=0.028), the CT genotype for rs3755751 (p=0.036), and G-allele carriers (AG plus GG) for rs40593 (p=0.015) exhibited a significant protective effect among those aged ≥45 years. For the haplotype analysis, ATS subjects aged ≥45 years had a higher frequency of the ACAC haplotype (76.0%) than the controls (68.1%; p<0.05); that haplotype was associated with an increased risk of ATS.ConclusionsThe obtained data suggest a positive association between MRAS and ATS among the Han Chinese. Further studies should be performed with larger sample and among different ethnic populations, and gene-gene or gene-environment interactions should be considered.

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

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

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