Genetic correlates of behavioral endophenotypes in Alzheimer disease:: Role of COMT, 5-HTTLPR and APOE polymorphisms
Genetic correlates of behavioral endophenotypes in Alzheimer disease:: Role of COMT, 5-HTTLPR and APOE polymorphisms
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DOI：
10.1016/j.neurobiolaging.2005.09.029
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Padovani, A.
中科院分区：
文献类型：
--
作者：
Borroni, B.;Grassi, M.;Padovani, A.
已经进行了几项研究，以了解阿尔茨海默病（AD）相关的痴呆（BPSD）行为和心理症状的遗传相关性。然而，鉴于BPSD很少孤立发生，有人建议，如果想要准确定义所有相关的风险因素，单独针对BPSD的方法过于狭隘。到目前为止，我们还没有发现与阿尔茨海默病行为内表型相关的遗传多态性。本研究旨在评估阿尔茨海默病的这些行为内表型与多巴胺或血清素相关基因的遗传变异之间的关系，如儿茶酚o -甲基转移酶（COMT）或5-羟色胺基因连锁启动子区域（5-HTTLPR）和载脂蛋白E （APOE）。232例AD患者接受了临床和神经心理学检查、行为和精神病学评估以及COMT、5-HTTPLR和APOE基因分型；66.4%表现出一种以上的行为症状。通过神经精神量表（NPI）症状的主成分分析，确定了四种内表型，这些被称为“精神病”、“情绪”、“冷漠”和“额叶”。通过潜在变量模型建模NPI症状-内表型-基因型关系，并考虑到可能的混杂因素（即人口统计学特征、合并症、伴随药物治疗和疾病严重程度），COMT和5-HTTLPR遗传变异与“额叶”和“精神病”内表型相关。APOE基因型与任何内表型均无相关性。这些发现表明，在AD患者中存在通过遗传基础识别不同表型的可能性，并提示将BPSD聚类为内表型可能为指导该问题的未来研究提供新的策略。(c) 2005爱思唯尔公司版权所有。
Several studies have been conducted to understand the genetic correlates of Alzheimer disease (AD)-related behavioral and psychological symptoms in dementia (BPSD). However, given that BPSD rarely occur in isolation, it has been suggested that targeting BPSD individually is too narrow of an approach if one wants to accurately define all the associated risk factors.To date, we know of no work on genetic polymorphisms related to behavioral endophenotypes in AD. The present study sought to evaluate the relationship between such behavioral endophenotypes in AD and genetic variations in dopamine- or serotonin-related genes, such as catechol-O-methyltransferase (COMT) or 5-HTT gene-linked promoter region (5-HTTLPR), and apolipoprotein E (APOE).Among 232 AD patients who underwent clinical and neuropsychological examination, a behavioral and psychiatric evaluation, and genotyping at COMT, 5-HTTPLR, and APOE; 66.4% showed more than one behavioral symptom. By Principal Component Analysis of Neuropsychiatric Inventory (NPI) symptoms four endophenotypes were identified, these were termed "psychosis", "moods", "apathy", and "frontal". Modeling NPI symptom-endophenotype-genotype relationships, and taking into account possible confounds (i.e. demographic characteristics, comorbidities, concomitant pharmacological treatments, and disease severity) by latent variable models, COMT and 5-HTTLPR genetic variations correlated with "frontal" and "psychosis" endophenotypes. APOE genotype did not correlate with any endophenotype.These findings suggest that the possibility of identifying distinct phenotypes on a genetic basis among AD patients exists, and suggest that clustering of BPSD into endophenotypes might provide a new strategy for guiding future research on this issue. (c) 2005 Elsevier Inc. All rights reserved.