新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » PLoS ONE报道 » PLoS ONE:与白内障、阿尔兹海默氏症相关的新基因

PLoS ONE:与白内障、阿尔兹海默氏症相关的新基因

来源:生物谷 2012-09-13 00:57

2012年9月13日 电 /生物谷BIOON/ --在一项最新的研究中,来自于波士顿大学医学院(BUSM)和公共卫生学院(BUSPH)的研究者发现了一种连接年龄相关的白内障和阿尔兹海默氏症两种病症的新型基因,这项研究发现刊登在了杂志PLoS One上,这或为治疗这两种疾病带来新的希望。

根据弗雷明汉后代眼部的研究相关信息(Framingham Offspring Eye Study cohort),研究者观察了其大脑MRI的信息或者是10年后其眼部检测的数据,最终研究者总结道,患者在白内障和阿尔兹海默氏症之间存在一定关联。

研究者随后展开了一项全基因组关联性研究,研究了将近190,000个单核苷酸多态性(SNPs)和DNA序列突变体。研究者在编码δ-连环蛋白的基因中发现了3个内含子SNPs,δ-连环蛋白是细胞吸附和形成接合结构的关键组分。以前有研究表明,该蛋白质和大脑、眼部发育相关,但是其并不与白内障或者阿尔兹海默症直接相关。

为了寻找其δ-连环蛋白和阿尔兹海默症的是否直接关联,研究者在顶级相关的SNPs附近转化入了一个突变的神经元δ-连环蛋白,使其形成了明显毒力增加的β淀粉样蛋白,β淀粉样蛋白就是阿尔兹海默氏症的标志性特点。另外研究者在阿尔兹海默症患者的晶状体结构处也发现了δ-连环蛋白水平的增加。

研究者Farrer表示,后续将会继续深入研究来使得开发出疾病早期的诊断方法以及针对两种疾病的新型疗法。(生物谷Bioon.com)

编译自:Gene Linking Cataracts and Alzheimer's Disease Identified

δ-Catenin Is Genetically and Biologically Associated with Cortical Cataract and Future Alzheimer-Related Structural and Functional Brain Changes

Gyungah Jun1,2,3*, Juliet A. Moncaster4, Carolina Koutras10, Sudha Seshadri5,8, Jacqueline Buros1, Ann C. McKee5,6,9,11, Georges Levesque12, Philip A. Wolf5,7,8, Peter St. George-Hyslop10,13, Lee E. Goldstein4,5,6,9, Lindsay A. Farrer1,2,3,5,7,9*

Multiple lines of evidence suggest that specific subtypes of age-related cataract (ARC) and Alzheimer disease (AD) are related etiologically. To identify shared genetic factors for ARC and AD, we estimated co-heritability of quantitative measures of cataract subtypes with AD-related brain MRI traits among 1,249 members of the Framingham Eye Study who had a brain MRI scan approximately ten years after the eye exam. Cortical cataract (CC) was found to be co-heritable with future development of AD and with several MRI traits, especially temporal horn volume (THV, ρ = 0.24, P<10−4). A genome-wide association study using 187,657 single nucleotide polymorphisms (SNPs) for the bivariate outcome of CC and THV identified genome-wide significant association with CTNND2 SNPs rs17183619, rs13155993 and rs13170756 (P<2.6×10−7). These SNPs were also significantly associated with bivariate outcomes of CC and scores on several highly heritable neuropsychological tests (5.7×10−9≤P<3.7×10−6). Statistical interaction was demonstrated between rs17183619 and APP SNP rs2096488 on CC (P = 0.0015) and CC-THV (P = 0.038). A rare CTNND2 missense mutation (G810R) 249 base pairs from rs17183619 altered δ-catenin localization and increased secreted amyloid-β1–42 in neuronal cell culture. Immunohistopathological analysis of lens tissue obtained from two autopsy-confirmed AD subjects and two non-AD controls revealed elevated expression of δ-catenin in epithelial and cortical regions of lenses from AD subjects compared to controls. Our findings suggest that genetic variation in delta catenin may underlie both cortical lens opacities in mid-life and subsequent MRI and cognitive changes that presage the development of AD.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库