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Int J Mol Epidemiol Genet 2012;3(3):245-251

Original Article
GDNF and BDNF gene interplay in chronic tinnitus

Sand PG, Langguth B, Schecklmann M, Kleinjung T

Department of Psychiatry, University of Regensburg, Germany; Department of Otorhinolaryngology, University of Zurich,

Received July 23, 2012; Accepted August 19, 2012; Epub August 31, 2012; Published September 15, 2012

Abstract: Background: Glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) play key
roles in the early development of the central auditory pathway and the inner ear. Both have been successfully employed to treat
experimental forms of hearing loss and are likely to operate in a broad spectrum of auditory phenotypes, including phantom
perceptions of sound. We conducted a genetic association study addressing five biallelic candidate variants in 240 Caucasian
subjects who had been diagnosed with tinnitus for more than 6 months. Findings: Allele frequencies were determined for three
GDNF and two BDNF markers, including a functional missense substitution (V66M). When data were compared to previously
examined control populations, no significant allelic associations were noted after corrections for multiple testing. However,
using a multiple regression approach and scores from a validated self-report questionnaire, GDNF and BDNF genotypes
jointly predicted tinnitus severity in women (N=69, uncorrected p=0.04) but not in men (N=171, n.s.). Conclusions: The present
findings serve as an incentive for further explorations of neurotrophic factors' role in predicting clinical features of tinnitus.
Possible implications of sexually dimorphic at-risk genotypes are discussed with regard to hearing and neural plasticity.

Keywords: BDNF, GDNF, tinnitus, sexual dimorphism, genetic variation

Address all correspondence to:
Dr. Philipp G. Sand
Department of Psychiatry
University of Regensburg, Universitaetsstrasse 84
93053 Regensburg, Germany.
Tel: +49 - 941 - 944 8955; Fax: + 49 - 941 - 944 8956
E-mail: philipp.sand@klinik.uni-regensburg.de