Clinical Interventions in Aging Dovepress a Genetic Screen of the Mutations in the Korean Patients with Early-onset Alzheimer's Disease-猫眼课题宝

DOI：

发表时间：

期刊：

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Seong Soo An;Ah Park;Eva Bagyinszky;Sunoh Bae;Yoon‐Jeong Kim;J. Im;Kyung Won Park;Kee Hyung Park;Eun-Joo Kim;Jee Hyang Jeong;Jong Hun Kim;Hyun Jeong;Hye Choi;Sangyun Kim

特此接受条款。未经Dove Medical Press Limited的进一步许可，允许对作品进行非商业用途，前提是该作品具有适当的属性。对于这项工作的商业使用许可，请参阅我们的条款摘要的第4.2和5段：早发性阿尔茨海默病（EOAD）与晚发性阿尔茨海默病（LOAD）相比具有独特的临床特征。遗传因素在EOAD中的作用更强。然而，EOAD中致病突变的频率可能因研究而异。此外，尚未在韩国进行大规模人群的突变筛查研究。之前，我们报道了在一项全国性的以医院为基础的队列研究中，EOAD患者的痴呆家族史率为18.7%，即韩国痴呆临床研究中心（CREDOS）研究。这一比率远低于其他国家，甚至与我国LOAD患者的频率相当。为了了解韩国EOAD的遗传特征，我们从2012年4月至2014年2月的CREDOS研究中筛选了连续EOAD受试者中常见的阿尔茨海默病（AD）突变。我们检查了APP（外显子16 - 17），PSEN 1（外显子3 - 12）和PSEN 2（外显子3 - 12）基因的序列。我们确定了不同的致病或可能致病的AD突变，PSEN 1 T116 I，PSEN 1 L226 F和PSEN 2 V214 L，采用24例有痴呆家族史的EOAD受试者和80例无痴呆家族史的受试者。PSEN 1 T116 I病例表现为常染色体显性遗传，在2代中至少有11个受影响个体。然而，在PSEN 1 L226 F和PSEN 2 V214 L病例中，一级亲属中没有痴呆家族史。约55.7%的EOAD患者携带APOE ε4等位基因，而携带突变的患者均未携带该等位基因。与其他国家的研究相比，本研究中的基因突变频率较低。基于全国队列的研究设计，最大限度地减少了选择偏倚，被认为是基因突变频率较低的原因之一。然而，不能排除韩国散发性AD较早发病的可能性更大。我们认为，在韩国EOAD人群中，AD早期发病和不携带APOE ε4等位基因是预测诱发基因突变的更可靠因素，而不是家族史的存在。

hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms Abstract: Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16−17), PSEN1 (exons 3−12), and PSEN2 (exons 3−12) genes. We identified different causative or probable pathogenic AD mutations , PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.

Clinical Interventions in Aging Dovepress a Genetic Screen of the Mutations in the Korean Patients with Early-onset Alzheimer's Disease

文献摘要

被引文献

相似文献