Association Analysis Of CNTNAP2, NRNX1, SHANK3 Polymorphism With Autism In Chinese Han Children

Autism is a pervasive developmental disorder mainly characterized by limited or absent verbal communication, lacking of reciprocal social interaction or responsiveness and restricted, stereotypical, and ritualized patterns of interests and behavior. Autism together with childhood disintegrative disorder, pervasive not otherwise specified (PDD-NOS, or atypical autism) and Asperger syndrome share the similar characteristics and are all included as autism spectrum disorder (ASD), also known as pervasive developmental disorder (PDD). The etiology is rather heterogeneous with the involvement of both genetic and nongenetic factors. Nevertheless, twin and family studies have indicated a primal role of genetic factors in the etiology of autism. In such studies, autism shows heritability as high as 80-90%. Autism was reported to affect approximately 0.11% of the population in China. Considering that the population is over 1.3 billion, autism presents a significant disease burden in China. Therefore, it is important to investigate the etiology of autism in the Chinese Han population. Synapses play an important role in the nervous system, the CNTNAP2, NRXN1 and SHANK3 related with the structure and function of synapses may be associated with autism that be demonstrated by some studies, so it is necessary to study the genes whether are autistic susceptible gene of the Chinese Han population. Methods:Before the chip technology is used for genotyping, we genotyped the three SNPs of CNTNAP2 gene in 161 autistic trios by using PCR-RFLP technique, then a family-based transmission disequilibrium test is performed by using haploview4.1 software. Furthermore, attempt to investigate association of CNTNAP2, NRXN1 and SHANK3 polymorphisms with autism in Chinese Han children; genotyping was carried out by using Illumina CNV 370-Duo chip in 280 autistic trios,455 autistic children and 97 controls.1000 controls were genotyped by using Illumina 610 chip in the Anhui Medical University. The genotype data of CNTNAP2,NRXN1,SHANKS were selected. Family based association studies and case-control was performed by using haploview 4.1 and haplotypes were constructed respectively.Results:1. The results of family association studies and case-control study showed that the rs7785603, rs10085579, rs2972110 of CNTNAP2 gene is associated with the increased risk for autism, and the haplotypes which included alleles of SNPs associated with autism also showed evidence of association.2. The results of family association studies and case-control study showed that the rs1518551, rs719645 of NRXN1 gene is associated with the increased risk for autism, and the haplotypes which included alleles of SNPs associated with autism also showed evidence of association.3. The results of family association studies and case-control study showed that the rs8137951 of SHANK3 gene is associated with the increased risk for autism, and haplotypes GA, AG of Block 2 also showed evidence of association.Conclusion:Our study showed that the genetic variability of CNTNAP2 gene, NRXN1 gene and SHANK3 gene are risk factors for autism in the Chinese Han population, which support the CNTNAP2 gene, NRXN1 gene and SHANK3 gene are susceptible gene of autism. Given the complex nature of a multifactorial neurodevelopmental disorders such as autism and the relatively small size of the study sample and their heterogeneity, further investigations, with larger sample size, are required to confirm whether the CNTNAP2 gene, NRXN1 gene and SHANK3 gene are associated with autism in the Chinese Han population.