Association Analysis Of DIP2A Polymorphisms And Dyslexia Susceptibility In Chinese Children

Objective: We aim to explore the association among gene polymorphisms of DIP2 A and dyslexia susceptibility in Chinese children, which could provide more understanding of the pathogenesis of dyslexia and scientific theory evidence for prevention and intervention.Methods: 1. A case-control study was conducted, which recruited 409 dyslexic children and 410 healthy controls who came from the ongoing Tongji Reading Environment and Dyslexia(READ) Study project. Their questionnaire information was statistically analyzed to explore the family environment factors associated with dyslexia.2. Genomic DNA was extracted from oral swab samples. The genetic variants in DIP2 A were selected by bioinformatics analysis and genotyping was performed with the Sequenom Mass ARRAY platform. A goodness-of-fit ?2 test was used to assess the Hardy–Weinberg equilibrium for genotypes. The differences in distribution of genotype frequencies and allele frequencies among cases and controls were examined by Pearson's ?2 test. The unconditional logistic regression was performed to evaluate the association between DIP2 A gene and dyslexia susceptibility. The statistical analyses were carried out with SPSS software(version 13.0).Results: 1. As thirteen DNA samples(including six dyslexics and seven controls) were not successfully genotyped, there was a sample of 403 dyslexics and 403 controls. The statistically significant differences were not found in the distribution of gender and age between the cases and controls(?2gender=0.010, Pgender=0.919; ?2age=0.852, Page=0.394).2. The results of structure equation model indicated that family's social economic status indirectly influenced the occurrence of dyslexia through home literacy environment. The comparative fit index(CFI), normed fit index(NFI) and root mean square error of approximation(RMSEA) respectively in this model were 0.976, 0.968, 0.058.3. According to the procedure for screening the candidate SNPs of DIP2 A gene and the results of genotyping, only rs2255526 and rs16979358 were remained for further analyzed. There was significant difference in the distribution of alleles frequencies of rs2255526 in DIP2 A gene between the cases and controls(?2=5.09, P=0.024). And there was no significant difference in the distribution of genotypes frequencies between the two groups. Significant differences in the distribution of both alleles and genotypes frequencies of rs16979358 were not found between the two groups(Ps>0.05). After adjusted for gender and age, there was a significantly increased dyslexia risk associated with rs2255526 GG genotypes(OR=1.833, 95%CI=1.043–3.223, P=0.035) and G allele(OR=1.297, 95%CI=1.036-1.623, P=0.023). In addition, it was marginally significantly associated with dyslexia under the dominant model(OR=1.314, 95%CI= 0.992-1.741, P=0.057) and the recessive model(OR=1.677, 95%CI=0.967-2.908, P=0.066). However, there was no evidence of an association of SNP rs16979358 with dyslexia.Conclusion: The study suggested that genetic variant in DIP2 A gene significantly increased developmental dyslexia risk in China.