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Effects of the BDNF Val66Met polymorphism on functional status and disability in young stroke patients
Robynne G Braun1, Steven J Kittner1,2, Kathleen A Ryan2
1University of Maryland School of Medicine, Baltimore, MD, United States of America.
Background And Purpose:
The preponderance of evidence from recent studies in human subjects supports a negative effect of the BDNF Val66Met polymorphism on motor outcomes and motor recovery. However prior studies have generally reported the effect of the Met allele in older stroke patients, while potential effects in younger stroke patients have remained essentially unexamined. The lack of research in younger patients is significant since aging effects on CNS repair and functional recovery after stroke are known to interact with the effects of genetic polymorphisms. Here we present a study of first-ever ischemic stroke patients aged 15-49 years that examines the effect of Met carrier status on functional disability.
Methods:
829 patients with a first ischemic stroke (Average age = 41.4 years, SD = 6.9) were recruited from the Baltimore-Washington region. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington. Our sample contained 165 Met carriers and 664 non-Met carriers. Modified Rankin scores as recorded at discharge were obtained from the hospital records by study personnel blinded to genotype, and binarized into "Good" versus "Poor" outcomes (mRS 0-2 vs. 3+), with mRS scores 3+ reflecting a degree of disability that causes loss of independence.
Results:
Our analysis showed that the Met allele conveyed a proportionally greater risk for poor outcomes and disability-related loss of independence with mRS scores 3+ (adjusted OR 1.73, 95% CI 1.13-2.64, p = 0.01).
Conclusions:
The BDNF Val66Met polymorphism was negatively associated with functional outcomes at discharge in our sample of 829 young stroke patients. This finding stands in contrast to what would be predicted under the tenets of the resource modulation hypothesis (i.e. that younger patients would be spared from the negative effect of the Met allele on recovery since it is posited to arise as a manifestation of age-related decline in physiologic resources).
Insights
The BDNF Val66Met polymorphism increases the risk of poor functional outcomes and disability after ischemic stroke in young adults. This finding challenges previous assumptions about age-related recovery from stroke.
Area of Science:
- Neuroscience
- Genetics
- Stroke Research
Background:
- The BDNF Val66Met polymorphism is linked to motor deficits in stroke patients.
- Previous research has primarily focused on older stroke patients, leaving the effects in younger populations understudied.
- Age-related factors are known to influence CNS repair and functional recovery, potentially interacting with genetic predispositions.
Purpose of the Study:
- To investigate the impact of the BDNF Val66Met polymorphism on functional outcomes in young ischemic stroke patients (aged 15-49).
- To examine the association between Met carrier status and functional disability at discharge.
Main Methods:
- A cohort of 829 first-ever ischemic stroke patients aged 15-49 years was analyzed.
- Genotyping for the BDNF Val66Met polymorphism was performed.
- Functional outcomes were assessed using modified Rankin Scale (mRS) scores at discharge, dichotomized into good (0-2) and poor (3+) outcomes.
Main Results:
- Met allele carriers had a significantly higher risk of poor functional outcomes and disability (mRS 3+) post-stroke.
- The adjusted odds ratio for poor outcomes in Met carriers was 1.73 (95% CI 1.13-2.64, p=0.01).
Conclusions:
- The BDNF Val66Met polymorphism is negatively associated with functional outcomes in young stroke survivors.
- This finding contradicts the resource modulation hypothesis, which predicted younger patients would be less affected by the Met allele's negative impact on recovery.
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