No association between polymorphisms in the BDNF gene and age at onset in Huntington disease

Maren Mai,Jörg T Epplen,Amer D Akkad,Carsten Saft,Larissa Arning,Jürgen Andrich,Peter H Kraus,Stefan Wieczorek

doi:10.1186/1471-2350-7-79

Maren Mai, Jörg T Epplen + Show 6 more

Open Access

https://doi.org/10.1186/1471-2350-7-79

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Abstract

BackgroundRecent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD). In particular, the functional Val66Met polymorphism appeared to exert a significant effect. Here we evaluate BDNF variability with respect to AO of HD using markers that represent the entire locus.MethodsFive selected tagging polymorphisms were genotyped across a 65 kb region comprising the BDNF gene in a well established cohort of 250 unrelated German HD patients.ResultsAddition of BDNF genotype variations or one of the marker haplotypes to the effect of CAG repeat lengths did not affect the variance of the AO.ConclusionWe were unable to verify a recently reported association between the functional Val66Met polymorphism in the BDNF gene and AO in HD. From our findings, we conclude that neither sequence variations in nor near the gene contribute significantly to the variance of AO.

Highlights

Recent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD)
We investigated the relation between the BDNF gene and the AO of HD using genetic markers that represent the overall variability at this locus
We examined the associations between BDNF polymorphisms and motor AO of HD in 250 unrelated patients with clinical diagnosis of HD as recruited from the Huntington Center (HZ) NRW, Bochum (Germany) [7]

Summary

Introduction

Recent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD). As the protein huntingtin (htt) directly modulates the expression of neuron-restrictive silencer factor (NRSF)-controlled genes, wild type (wt) htt stimulates the production of BDNF, whereas mutant htt causes the opposite effect [1]. It has been shown recently in transgenic mice that BDNF has an impact on the age at onset (AO) and the severity of motor dysfunction by controlling survival of striatal projection neurons [2]. Met-BDNF carriers demonstrate substantial relative (page number not for citation purposes)

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Conclusion