Cassidy Michael R, Roberts J Scott, Bird Thomas D, Steinbart Ellen J, Cupples L Adrienne, Chen Clara A, Linnenbringer Erin, Green Robert C
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Alzheimers Dement. 2008 Nov;4(6):406-13. doi: 10.1016/j.jalz.2008.04.007.
Genetic risk for Alzheimer's disease (AD) can be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the epsilon 4 allele increases the risk of developing late-onset AD but is not a definitive predictor of the disease, or by autosomal dominant mutations (eg, the presenilins), which almost inevitably result in early-onset familial AD. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.
Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for AD with APOE in 101 adult children of AD patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial AD or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the impact of event scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to 1 year after disclosure at which IES data were available. The role of genetic test result (positive vs negative) and type of genetic testing (deterministic vs susceptibility) in predicting log-transformed IES scores were assessed with linear regression, controlling for age, gender, and time from disclosure.
Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE epsilon 4+ experienced similar, low levels of test-specific distress compared with those who received positive results of deterministic testing in the University of Washington study (P = .78). APOE epsilon 4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested epsilon 4- in the same study (P = .04); however, among those receiving deterministic test disclosure, the subjects who received positive results did not experience significantly higher levels of distress when compared with those who received negative results (P = .88).
The findings of this preliminary study, with limited sample size, suggest that the test-related distress experienced by those receiving positive results for a deterministic mutation is similar to the distress experienced by those receiving positive results from genetic susceptibility testing, and that the majority of participants receiving genotype disclosure do not experience clinically significant distress as indicated by IES scores 1 year after learning of their test results.
阿尔茨海默病（AD）的遗传风险可由易感性多态性载脂蛋白E（APOE）赋予，其中ε4等位基因增加了患晚发性AD的风险，但并非该病的确切预测指标；或者由常染色体显性突变（如早老素）导致，这种突变几乎不可避免地会引发早发性家族性AD。本研究的目的是比较使用这两种不同类型的基因信息向AD患者家属披露AD遗传风险所产生的心理影响。
对两个独立方案的数据进行比较。阿尔茨海默病风险评估与教育（REVEAL）研究是一项随机、多中心临床试验，评估了对101名AD患者成年子女进行APOE AD易感性检测的影响。华盛顿大学进行的另一项研究评估了向22名有家族性AD或额颞叶痴呆风险的个体披露早老素-1、早老素-2或TAU基因型的确定性基因检测的影响。在这两个方案中，参与者都接受了遗传咨询，并完成了事件影响量表（IES），这是一种针对检测特异性痛苦的测量方法。在披露后最接近1年且有IES数据的时间点对分数进行分析。通过线性回归评估基因检测结果（阳性与阴性）和基因检测类型（确定性与易感性）在预测对数转换后的IES分数中的作用，并控制年龄、性别和披露后的时间。
与在华盛顿大学研究中接受确定性检测阳性结果的受试者相比，REVEAL研究中得知自己APOE ε4基因易感性检测呈阳性的受试者经历了相似的、较低水平的检测特异性痛苦（P = 0.78）。易感性方案中的APOE ε4+个体比同一研究中检测为ε4-的个体经历了更多的检测特异性痛苦（P = 0.04）；然而，在接受确定性检测披露的受试者中，与接受阴性结果的受试者相比，接受阳性结果的受试者并未经历显著更高水平的痛苦（P = 0.88）。
这项样本量有限的初步研究结果表明，接受确定性突变阳性结果的受试者所经历的检测相关痛苦与接受遗传易感性检测阳性结果的受试者所经历的痛苦相似，并且大多数接受基因型披露的参与者在得知检测结果1年后，根据IES分数显示并未经历临床上显著的痛苦。
