DNMT3B Promoter Polymorphisms and Risk of Late Onset Alzheimer's Disease
DNMT3B Promoter Polymorphisms and Risk of Late Onset Alzheimer's Disease
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DOI：
10.2174/156720512800618062
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发表时间：
2012-06-01
影响因子：
2.1
通讯作者：
Migliore, Lucia
中科院分区：
文献类型：
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作者：
Coppede, Fabio;Zitarosa, Maria Teresa;Migliore, Lucia
绝大多数阿尔茨海默病(AD)是迟发性的形式(负荷)，可能是由于遗传、环境和随机因素的贡献，叠加在与年龄相关的生理性神经功能下降上。越来越多的证据表明，负荷脑的表观遗传修饰，以及许多与AD风险相关的环境因素，如重金属和饮食因素，都能够修改表观基因组。也有迹象表明，在胚胎发生和大脑发育期间，环境诱导的早期生命对基因组的修改可能有助于疾病在以后的生命中发展。DNA甲基转移酶3b(Dnmt3b)是一种参与胚胎发育过程中基因组去重甲基化的酶，在神经发生过程中在祖细胞中表达。在本研究中，我们评估了两个功能性Dnmt3b启动子多态性，即-149C>；T(Rs2424913)和-579G>；T(Rs1569686)，作为候选负荷危险因素。我们对376名意大利LOAD患者和308名匹配的对照组的分析表明，病例组和对照组之间的等位基因频率没有差异(rs2424913的OR=1.10(0.88-1.39)，rs1569686的OR=1.02(0.81-1.28))。两种多态基因在组间的分布也非常相似，对发病年龄无显著影响。总体而言，目前的结果不支持rs2424913或rs1569686在LOAD发病机制中的主要作用。
The vast majority of Alzheimer's disease (AD) are late-onset forms (LOAD) likely due to the contribution of genetic, environmental, and stochastic factors, superimposed on a physiologically age-related decline of neuronal functions. Increasing evidence indicates epigenetic modifications in LOAD brains, and many of the environmental factors associated with AD risk, such as heavy metals and dietary factors, are able to modify the epigenome. There is also indication that environmentally-induced early life modifications of the genome during embryogenesis and brain development could contribute to the development of the disease later in life. DNA methyltransferase 3b (DNMT3b) is an enzyme involved in de novo methylation of the genome during embryogenesis, expressed in progenitor cells during neurogenesis. In the present study we evaluated two functional DNMT3B promoter polymorphisms, namely -149 C>T (rs2424913) and - 579 G>T (rs1569686), as candidate LOAD risk factors. Our analysis of 376 Italian LOAD patients and 308 matched controls revealed no difference in allele frequencies between the case an the control group (OR = 1.10 (0.88-1.39) for rs2424913, and OR = 1.02 (0.81-1.28) for rs1569686). Also the genotype distributions of both polymorphisms were closely similar between groups, and no significant effect on disease age at onset was observed. Overall, present results do not support a major role for rs2424913 or rs1569686 in LOAD pathogenesis.