ASSOCIATION STUDY OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NEURAL CELL ADHESION MOLECULE (NRCAM) POLYMORPHISMS WITH FRENCH AUTISTIC PATIENTS

Background: Differences in the serum levels of brain-derived neurotrophic factor (BDNF) were observed between patients with autism compared to controls. Furthermore, haplotypes of BDNF gene were associated with autism by transmission disequilibrium test. And, variants of neural cell adhesion molecule NRCAM gene were found associated with autism in different reports.

Objectives: Study the genetic association between BDNF and NRCAM polymorphisms with autism in a French population.

Methods: The BDNF gene is located on chromosome 11p13 and corresponds to one haplotype block only. While the NRCAM gene is mapped on chromosome 7q31.1-q31.2 region and is encompassed by several haplotype block We performed a case-control study by genotyping two SNPs (the missense rs6265 and rs11030121) within BDNF gene, and the missense rs6958498 within NRCAM gene, using TaqMan® SNP Genotyping Assays, on 84 French autistic patients and 143 healthy controls matching for the geographic origin. Hardy-Weinberg equilibrium of SNPs was checked by using Haploview software. Distributions of alleles, genotypes and carriers were compared between patients and controls by crosstabs analysis.

Results: Each SNP followed the Hardy-Weinberg equilibrium. No significant difference of frequency for rs6265 or rs11030121 was found in patients compared to controls (81% versus 83% and 68% versus 72%, respectively for each major allele). Furthermore, no difference of distribution was found with the genotypes and carriers of each SNPs, nor with the haplotype rs6265-rs11030121. In contrast, we found a trend for association between NRCAM polymorphism and autism with an overrepresentation of the C allele (84.7% versus 77.3%, Fisher’s exact test 2-sided p=0.1), corresponding to the proline amino acid.

Conclusions: This genetic analysis, on a population originating from France, does not support the association between BDNF gene and autism but suggests the involvement of NRCAM gene in autism.