Association between BDNF Val66Met polymorphism and age at onset in Huntington disease

Huntington disease (HD) is caused by CAG repeat expansion in exon 1 of the IT15 gene, which encodes huntingtin protein. The influence of expanded CAG repeats on the age at onset is clear in the case of low and high number of repeats, but the predictive value is weaker in intermediate ranges.1 Therefore, environmental factors, sex, or interacting genes may alter the course of the disease.1 Although a genome scan report did not link the age at onset with BDNF region,2 other studies have shown that huntingtin functions as a positive regulator of BDNF transcription.3 This may explain the decrease in BDNF levels reported in patients with HD.3 Furthermore, BDNF levels modulate the age at onset in transgenic models.4 Recently, the presence of a polymorphism in the BDNF gene leading to a valine (val) to methionine (met) substitution at position 66 in the BDNF prodomain (Val66Met) has been correlated with deleterious5 or beneficial6 effects in several neuropsychiatric diseases. Here we studied the effect of BDNF on the age at onset, analyzing the relationship of the Val66Met polymorphism and CAG repeat number in patients …