Published Online
on August 30, 2007

A more recent version of this article appeared on October 1, 2007

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Submitted on February 24, 2007
Revised on April 12, 2007
Accepted on April 17, 2007

The Met Allele of the BDNF Val66Met Polymorphism Predicts Poor Outcome Among Survivors of Aneurysmal Subarachnoid Hemorrhage

Jari Siironen MD, PhD^*; Seppo Juvela MD, PhD; Katarzyna Kanarek MS; Juhani Vilkki PhD; Juha Hernesniemi MD, PhD; and Jaakko Lappalainen MD, PhD

From the Department of Neurosurgery (J.S., S.J., J.V., J.H.), Helsinki University Central Hospital, Finland; the Department of Neurosurgery (S.J.), Turku University Central Hospital, Finland; and the Department of Psychiatry (K.K., J.L.), Yale University School of Medicine, Connecticut, USA and VA Connecticut Healthcare System, West Haven, Connecticut, USA.

^* To whom correspondence should be addressed. E-mail: jari.siironen{at}mac.com.

Background and Purpose—Brain-derived neurotrophic factor (BDNF) plays a role in neuronal survival, plasticity and neurogenesis. The BDNF gene contains a common Val66Met polymorphism; the Met allele is associated with lower depolarization-induced BDNF release and differences in memory functions and brain morphology. We hypothesized that the Met allele is associated with poor recovery from subarachnoid hemorrhage.

Methods—A sample of 105 survivors was assessed at 3 months after subarachnoid hemorrhage using Glascow Outcome Scale. Poor outcome was defined as severe disability or worse. DNA samples were genotyped for the Val66Met polymorphism.

Results—Higher percentage of the Met carriers had a poor outcome (29%) as compared with the Val/Val group (10%; P=0.011). In multiple logistic regression, this association between the Met allele and poor outcome was independent of several other prognostic factors such as patient age, clinical condition, and radiological severity of the bleeding (odds ratio 8.40; 95% CI, 1.60 to 44.00; P=0.012).

Conclusions—Genetically influenced variation in BDNF function plays a role in recovery from subarachnoid hemorrhage. These data indicate that augmentation of BDNF signaling may be beneficial to recovery from brain injury.

Key words: BDNF • polymorphism • outcome • SAH

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