Possible shared genetic risk factors for Gilles de la Tourette syndrome and obsessive compulsive behaviour: the Val66Met polymorphism of the brain derived neurotrophic factor (BDNF)

Objective: To evaluate a possible association of the Valine66Methionine (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF) gene [MIM113505] with Gilles de la Tourette syndrome (GTS) by genotyping the single nucleotide polymorphism (SNP) for the G->A polymorphism at position 758 of the BDNF coding sequence in 88 GTS trios.

Background: BDNF is a member of the neurotrophin superfamily promoting cell survival and neuronal differentiation. A significant association of the Val66Met polymorphism of BDNF in patients with childhood-onset obsessive-compulsive disorder (OCD) was recently described. In particular, undertransmission of the rare Met66 allele was observed and it was speculated that this allele might confer a protective effect for OCD [1]. OCD occurs in up to 50% of GTS patients and is therefore considerably more common in GTS than in the normal population. Furthermore, clinico-genetic studies suggest a shared genetic susceptibility factor for both GTS and OCD in at least some families. We investigated whether the Met66 allele is not only undertransmitted in OCD, but also in GTS.

Methods: 88 patients with GTS (77 male, 11 female, mean age at onset 6.3±2.6 years) and both their parents were ascertained at four University Departments of Child and Adolescent Psychiatry in Germany. The Val66Met polymorphism was genotyped as previously described [1]. The extended transmission/disequilibrium test (ETDT) was applied to analyse the transmission rates.

Results: Transmission rates for both the Met66 and the Val66 alleles in the GTS trios included in our study did not differ from the expected transmission rates (chi2=0.67, p=0.41 for all 88 GTS trios; chi2=0.92, p=0.34 when only GTS families without concomitant OCD were included; the number of GTS trios with concomitant OCD was not large enough to allow independent subgroup analysis for this group).

Conclusion: The previously described association of the BDNF Val66Met polymorphism with OCD resulting in an undertransmission of the Met66 allele was not observed in 88 trios with GTS. Thus, the Val66Met polymorphism does not seem to be a genetic risk factor for GTS. Further investigations are necessary to identify distinct genetic risk factors for this disease.

References:

1.Hall D, Dhilla A, Charalambous A et al. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive compulsive disorder. Am J Hum Genet 2003,73:370–376.