BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson's disease

• Published in: European journal of neurology Vol. 16; no. 11; pp. 1240 - 1245
• Main Authors: Guerini, F. R., Beghi, E., Riboldazzi, G., Zangaglia, R., Pianezzola, C., Bono, G., Casali, C., Di Lorenzo, C., Agliardi, C., Nappi, G., Clerici, M., Martignoni, E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2009
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Brain Derived Neurotrophic Factor; Brain-Derived Neurotrophic Factor - genetics; Chi-Square Distribution; Cognition Disorders - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Italy; Male; Middle Aged; Mini Mental State Examination; Neuropsychological Tests; Parkinson Disease - genetics; Parkinson's disease; Polymorphism, Single Nucleotide - genetics; Regression Analysis; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Italy
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/j.1468-1331.2009.02706.x

Background and purpose:  A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients.
Methods:  The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score.
Results:  Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment.
Conclusions:  The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.