基因君官网
2015年12月17日讯/生物谷BIOON/科学家们确定了9个基因形成的网状物对阿尔茨海默病的发病起着非常重要的作用。
澳大利亚国立大学首席研究员Mauricio Arcos-Burgos说，这一发现可以帮助科学家开发新疗法用来延缓疾病的发作。
在哥伦比亚一项家族研究中，通过对5000人的研究，科学家们发现了延迟疾病发展的基因。
“如果你能找出怎样减缓该病的方法，就会产生深远的意义。”约翰科廷医学研究学院(JCSMR) 医学遗传学家Arcos-Burgos副教授说。
“我认为推迟疾病的发病比完全阻止疾病发生将更有可能实现。即使我们推迟发病一年，这将意味着在2050年时可阻止九百万人发病。”
阿尔茨海默氏症影响世界各地约3500万人，预计到2050年会影响85分之一的人。
哥伦布家族受到一种遗传性阿尔茨海默氏症的困扰。它们是对抗疾病的唯一一种独特的资源，因为他们生活在哥伦比亚西部山区一个特定地区的强大且紧密的家族。
美国国立卫生研究所已经把1.7亿美元用于治疗阿尔茨海默氏症，这些费用将在这个家族中被用来进行测试。
Arcos-Burgos副教授和他的研究组采取了不同的方法研究了这个家族老年痴呆症的发病年龄，而不是在以后的生活中试图治疗症状的发展，因为即使在20岁之前也可以观察到个体大脑的变化。
研究组与家族合作能够分析环境因素并跟踪他们阿尔茨海默病的遗传易感性。
研究组能够隔离阿尔茨海默氏症中的9个基因，其中一些基因延迟发病17年，而其它一些基因可推进其进程。这项研究发表在《分子精神病学》。（基因宝jiyinbao.com）
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APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease
J I Vélez1,2,12, F Lopera2,12, D Sepulveda-Falla2,3,12, H R Patel1, A S Johar1, A Chuah4, C Tobón2, D Rivera2, A Villegas2, Y Cai1, K Peng5, R Arkell6, F X Castellanos7,8, S J Andrews9, M F Silva Lara1, P K Creagh1, S Easteal9, J de Leon10, M L Wong11, J Licinio11,12, C A Mastronardi1,11,12 and M Arcos-Burgos1,2,12
Alzheimer’s disease (AD) age of onset (ADAOO) varies greatly between individuals, with unique causal mutations suggesting the role of modifying genetic and environmental interactions. We analyzed ~50 000 common and rare functional genomic variants from 71 individuals of the ‘Paisa’ pedigree, the world’s largest pedigree segregating a severe form of early-onset AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene. Affected carriers with ages at the extremes of the ADAOO distribution (30s–70s age range), and linear mixed-effects models were used to build single-locus regression models outlining the ADAOO. We identified the rs7412 (APOE*E2 allele) as a whole exome-wide ADAOO modifier that delays ADAOO by ~12 years (β=11.74, 95% confidence interval (CI): 8.07–15.41, P=6.31 × 10−8, PFDR=2.48 × 10−3). Subsequently, to evaluate comprehensively the APOE (apolipoprotein E) haplotype variants (E1/E2/E3/E4), the markers rs7412 and rs429358 were genotyped in 93 AD affected carriers of the E280A mutation. We found that the APOE*E2 allele, and not APOE*E4, modifies ADAOO in carriers of the E280A mutation (β=8.24, 95% CI: 4.45–12.01, P=3.84 × 10−5). Exploratory linear mixed-effects multilocus analysis suggested that other functional variants harbored in genes involved in cell proliferation, protein degradation, apoptotic and immune dysregulation processes (i.e., GPR20, TRIM22, FCRL5, AOAH, PINLYP, IFI16, RC3H1 and DFNA5) might interact with the APOE*E2 allele. Interestingly, suggestive evidence as an ADAOO modifier was found for one of these variants (GPR20) in a set of patients with sporadic AD from the Paisa genetic isolate. This is the first study demonstrating that the APOE*E2 allele modifies the natural history of AD typified by the age of onset in E280A mutation carriers. To the best of our knowledge, this is the largest analyzed sample of patients with a unique mutation sharing uniform environment. Formal replication of our results in other populations and in other forms of AD will be crucial for prediction, follow-up and presumably developing new therapeutic strategies for patients either at risk or affected by AD.