Association of a variation in the promoter region of the brain-derived neurotrophic factor gene with familial Parkinson's disease.

Genes coding for nerve growth factors involved in dopamine receptor and cellular regulation such as brain-derived neurotrophic factor (BDNF) are logical candidate genes for susceptibility to Parkinson's disease (PD). To determine the role of the BDNF gene in the development of familial and sporadic PD, we sequenced the promoter region of the gene using genomic DNA from patients with familial PD. Two single nucleotide polymorphisms (SNPs) at positions C-1331T and C270T were identified. We screened our samples with the SNPs at C270T and G196A in the gene. The 270T allele was more common in the familial PD subjects compared to normal controls (p = 0.0006) but not significantly different between sporadic PD and normal controls. The genotype frequencies were significantly different only between familial PD and normal controls (p = 0.00001). There was also a highly significant difference in allele and genotype frequency between the familial group with age of onset of >50 years and controls (p = 0.0002 and p = 0.0001). We estimated and compared the haplotype frequencies between C270T and G196A markers in PD and controls that was positive (p = 0.0019). All positive results remain significant after Bonferroni's correction. Our data indicate the possibility of linkage disequilibrium between the C270T variation and a mutation in coding region of the BDNF gene and suggest that this gene may play a role in the development of familial PD.