Disclosure of APOE Genotype for Risk of Alzheimer's Disease

作者：Green Robert C^*; Roberts J Scott; Cupples L Adrienne; Relkin Norman R; Whitehouse Peter J; Brown Tamsen; Eckert Susan LaRusse; Butson Melissa; Sadovnick A Dessa; Quaid Kimberly A; Chen Clara; Cook Deegan Robert; Farrer Lindsay A

来源：New England Journal of Medicine, 2009, 361(3): 245-254.

DOI：10.1056/NEJMoa0809578

Background
The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.
Methods
We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.
Results
There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P = 0.84), depression (8.8 and 8.7, respectively; P = 0.98), or test-related distress (6.9 and 7.5, respectively; P = 0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon 4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon 4-negative subgroup had a significantly lower level of test-related distress than did the epsilon 4-positive subgroup (P = 0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon 4-positive and epsilon 4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).
Conclusions
The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon 4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

• 出版日期2009-7-16