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DNA甲基转移酶基因多态性与帕金森病之间的关联。

Association between DNA methyltransferase gene polymorphism and Parkinson's disease.

作者信息

Pezzi Julio Carlos, de Bem Cintia Monique Boschmann Ens, da Rocha Tatiane Jacobsen, Schumacher-Schuh Artur F, Chaves Marcia Lorena Fagundes, Rieder Carlos Roberto, Hutz Mara H, Fiegenbaum Marilu, Camozzato Ana Luiza

机构信息

Postgraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.

Postgraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.

出版信息

Neurosci Lett. 2017 Feb 3;639:146-150. doi: 10.1016/j.neulet.2016.12.058. Epub 2016 Dec 29.

Abstract

Parkinson's disease (PD) is a common and complex neurodegenerative disorder, the second most prevalent, only behind Alzheimer's disease. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, that is carried out by enzymes, such as DNMT1 and DNMT3B. This present study targeted to investigate the association among DNMT1 and DNMT3B polymorphisms with PD. Five hundred and twenty-two participants (214 PD patients following UK Brain Bank criteria and 308 healthy individuals) were evaluated. DNA was obtained from whole blood and genotypes were detected by an allelic discrimination assay using TaqMan MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560 and rs759920 (DNMT1) and rs2424913, rs998382 and rs2424932 (DNMT3B). Was found association between DNMT3B rs2424913 in T allele carriers with PD. The presence of the T allele was associated with PD (OR=1.80, 95% CI 1.16-2.81, p=0.009). No significant difference was observed for others DNMT3B SNPs. Also, no association between PD and the control group were observed for DNMT1 polymorphisms. This is the first study addressing an association between DNMT3B polymorphism and PD. The polymorphism may play a role in the pathogenesis of PD.

摘要

帕金森病(PD)是一种常见且复杂的神经退行性疾病,其患病率仅次于阿尔茨海默病,位居第二。近期研究表明,环境因素可能通过诱导表观遗传修饰(如由DNMT1和DNMT3B等酶进行的DNA甲基化)来促成神经退行性变。本研究旨在调查DNMT1和DNMT3B基因多态性与帕金森病之间的关联。对522名参与者(214名符合英国脑库标准的帕金森病患者和308名健康个体)进行了评估。从全血中提取DNA,并使用TaqMan MGB探针在实时PCR系统上通过等位基因鉴别分析检测基因型。所研究的多态性包括rs2162560和rs759920(DNMT1)以及rs2424913、rs998382和rs2424932(DNMT3B)。发现DNMT3B的rs2424913中T等位基因携带者与帕金森病之间存在关联。T等位基因的存在与帕金森病相关(比值比=1.80,95%可信区间1.16 - 2.81,p = 0.009)。对于其他DNMT3B单核苷酸多态性未观察到显著差异。此外,对于DNMT1基因多态性,在帕金森病患者和对照组之间未观察到关联。这是第一项探讨DNMT3B基因多态性与帕金森病之间关联的研究。该多态性可能在帕金森病的发病机制中起作用。

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