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微粒体()和可溶性环氧化物水解酶()的错义基因多态性及其与土耳其人群中大动脉粥样硬化性缺血性中风风险的关系。

Missense Genetic Polymorphisms of Microsomal () and Soluble Epoxide Hydrolase () and Their Relation to the Risk of Large Artery Atherosclerotic Ischemic Stroke in a Turkish Population.

作者信息

Can Demirdöğen Birsen, Miçooğulları Yağmur, Türkanoğlu Özçelik Aysun, Adalı Orhan

机构信息

Department of Biomedical Engineering, TOBB University of Economics and Technology, Ankara, Turkey.

Institute of Natural and Applied Sciences, Department of Biology, Middle East Technical University, Ankara, Turkey.

出版信息

Neuropsychiatr Dis Treat. 2021 May 7;16:3251-3265. doi: 10.2147/NDT.S233992. eCollection 2020.

Abstract

PURPOSE

Soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH) both catalyze the metabolism of epoxyeicosatrienoic acids (EETs), lipid signaling molecules that are protective against ischemic brain injury owing to their participation in the regulation of vascular tone and cerebral blood flow. In addition, mEH metabolizes polycyclic aromatic hydrocarbons, one of the causative factors of atherosclerotic lesion development. In this study, we aimed to investigate the association of enzyme activity-modifying missense single nucleotide polymorphisms (SNPs) of the sEH gene () and mEH gene () and ischemic stroke risk in a Turkish population.

PATIENTS AND METHODS

Genomic DNA of patients with large artery atherosclerotic ischemic stroke (n=237) and controls (n=120) was isolated from blood samples, and genotypes for Tyr113His (rs1051740) and His139Arg (rs2234922) SNPs of and Arg287Gln (rs751141) SNP of were attained by the PCR/RFLP method.

RESULTS

Minor allele frequency and genotype distributions for Arg287Gln, Tyr113His and His139Arg SNPs did not differ significantly between stroke patients and controls. However, hypertension- and diabetes-associated ischemic stroke risk was decreased by and increased by variants in stratification analyses.

CONCLUSION

This study has shown for the first time that the polymorphic alleles of were unlikely to be associated with large artery atherosclerotic ischemic stroke susceptibility; however, protective effects were evident within subgroups of hypertension and diabetes. In addition, Arg287Gln polymorphism, which has been studied for the first time in a Turkish population, was not significantly related to ischemic stroke, but increased the stroke risk in subgroup analysis.

摘要

目的

可溶性环氧化物水解酶(sEH)和微粒体环氧化物水解酶(mEH)均催化环氧二十碳三烯酸(EETs)的代谢,EETs是一类脂质信号分子,因其参与血管张力和脑血流量的调节而对缺血性脑损伤具有保护作用。此外,mEH还代谢多环芳烃,这是动脉粥样硬化病变发展的致病因素之一。在本研究中,我们旨在调查土耳其人群中sEH基因()和mEH基因()的酶活性修饰错义单核苷酸多态性(SNPs)与缺血性中风风险的关联。

患者与方法

从血液样本中分离出大动脉粥样硬化性缺血性中风患者(n = 237)和对照组(n = 120)的基因组DNA,并通过PCR/RFLP方法获得sEH基因的Tyr113His(rs1051740)和His139Arg(rs2234922)SNPs以及mEH基因的Arg287Gln(rs751141)SNP的基因型。

结果

中风患者和对照组之间,Arg287Gln、Tyr113His和His139Arg SNPs的次要等位基因频率和基因型分布没有显著差异。然而,在分层分析中,高血压和糖尿病相关的缺血性中风风险分别因sEH基因变异降低和因mEH基因变异增加。

结论

本研究首次表明,sEH基因的多态性等位基因不太可能与大动脉粥样硬化性缺血性中风易感性相关;然而,在高血压和糖尿病亚组中保护作用明显。此外,首次在土耳其人群中研究的mEH基因Arg287Gln多态性与缺血性中风无显著相关性,但在亚组分析中增加了中风风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/428b/8114577/bc92628815ab/NDT-16-3251-g0001.jpg

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