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Allelic Differences in the Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Late-Life Depression

From the Departments of Psychiatry (WDT, SZ, DRM, DCS, KRRK) and Medicine (MCS), and The Center for Human Genetics (WDT, MCS), Duke University Medical Center, Durham, NC.

Objective: The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with cognitive and neuroimaging changes. The authors examined the relationship between this polymorphism and depression in an elderly sample, hypothesizing that the Met66 allele would be associated with late-life depression.

Methods: A total of 245 elderly depressed white subjects and 94 elderly comparison white subjects completed clinical assessments and provided a blood sample for genotyping. Subjects were dichotomized as either homozygous for the Val66 allele or Met66 allele carriers. Gene frequencies were compared between groups, with separate analyses examining for differences in gene frequencies based on age of depression onset, family history, and depression history. Logistic regression models examined the relationship between genotype and depression after controlling for age, sex, and race.

Results: Depressed subjects were more likely to be Met66 allele carriers than were comparison subjects (38.8% versus 24.4%; ² = 6.13, 1 df, p = 0.0133). This relationship remained significant after controlling for covariates (Wald ² = 5.10, 1 df, p = 0.024; odds ratio: 1.92, 95% confidence interval: 1.09–3.38). There were no significant relationships between genotype and age of onset, number of episodes, or family history of depression.

Conclusion: Met66 allele carriers have almost double the odds of having geriatric depression than do Val66 allele homozygotes. This polymorphism was unrelated to other clinical characteristics of depression in later life.

Key Words: Single nucleotide polymorphism • depression • gene frequency

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				W. D. Taylor, S. Zuchner, D. R. McQuoid, M. E. Payne, J. R. MacFall, D. C. Steffens, M. C. Speer, and K. R. R. Krishnan The Brain-Derived Neurotrophic Factor VAL66MET Polymorphism and Cerebral White Matter Hyperintensities in Late-Life Depression Am J Geriatr Psychiatry, April 1, 2008; 16(4): 263 - 271. [Abstract] [Full Text] [PDF]