Association of NCAM1 polymorphisms with autism and parental age at conception in a Chinese Han population

Abstract

Aims: The neural cell adhesion molecule (NCAM) has been reported to be involved in the development of the central nervous system and its mRNA level might decrease in the serum of autistic patients. However, there was no evidence of the association of the NCAM1 gene polymorphisms with autism. In the present study, we enrolled 237 children with autism and 451 healthy control subjects. Then, we used the direct DNA sequencing for genotyping five tag single-nucleotide polymorphisms (SNPs) in the NCAM1 gene.

Results: By using case-control association analyses, we found that three SNPs at the NCAM1 gene were associated with autism (rs 4937786, p=0.015; rs 12418058, p=0.0076; rs 1436109, p=0.0023). Two of them remained significant after the Bonferroni multiple testing correction (rs 12418058, P(corrected) =0.038; rs 1436109, P(corrected) =0.012). Moreover, two of the SNPs were associated with the parental age at conception in autism (rs 12418058, p=0.037; rs 1436109, p=0.01).

Conclusion: These results showed that NCAM1 might play an important role in the pathogenesis of autism.

FIG. 1.

The linkage disequilibrium (LD) structure of the regions of five tag SNPs of NCAM1 gene, according to the Haploview (solid spine of LD, D′>0.7; www.broad.mit.edu/mpg/haploview/). Markers with LD (D′<1 and LOD>2) are shown in black through grey (color intensity decreases with decreasing D′ value). Regions of low LD and low LOD scores (D′<1 and LOD>2) are shown in white.