GDNF and BDNF gene interplay in chronic tinnitus.

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.