An Association Study Between Synaptosomal-associated Protein 25 Gene Polymorphisms And Attention Deficit Hyperactivity Disorder

Objective: To explored the potential associations between synaptosomal-associated protein 25 gene polymorphisms and children ADHD in Han Chinese in order to provide theoretical evidences for the pathogenesis of ADHD.Methods:(1) Association Study: According to the case-control design, 192 ADHD cases based on DSM-IV diagnostic criteria and 192 healthy controls were collected in the same period in Hunan Provincial Children’s Hospital. Collect each subject 2ml venous blood, as well as the basic demographic information. Genotyping analyses were performed for rs3746544 and rs363006 at Sequenom Mass Array gene platform after DNA extraction. Chi-square test of SPSS was applied for the bias detection between the cases and controls of the genotypes or alleles of rs3746544 and rs363006.(2) Meta-analysis: The Pubmed, Embase, Google Scholar database in English and CNKI database in Chinese were applied to find out all the literatures in doing association study between SNAP-25 and ADHD. Study quality was assessed by Strengthening the Reporting of Genetic Association studie(STREGA). Extract data from all association studies between rs3746544 or rs363006 and ADHD, and then do the summarised estimation of the odds ratio(OR) and 95% confidence interval(CI) and draw forest plots by the metafor package of R software. Additionally, do a comprehensive meta-analysis including the rest of the single nucleotide polymorphisms(rs10511312, rs8636, rs362549, rs362998) of SNAP-25 for the association with ADHD.Results:(1) Association Study: Rs3746544 and rs363006 in controls are both in accordance with HWE. Rs3746544 A allele carrier have a higher risk of ADHD than C allele(OR=1.60, 95%CI=1.10-2.32, P=0.013), however no association was found between rs363006 and ADHD(OR=0.92, 95%CI=0.59-1.42, P=0.692).(2) Meta-analysis: Rs3746544 T or A allele carrier have a higher risk of ADHD than G or C allele(OR=1.20, 95%CI=1.05-1.37, P=0.008), however no association was found between rs363006 and ADHD(OR=1.02, 95%CI=0.86-1.21, P=0.805). The meta-analysis results were in accordance with the association study results. Additionally, no association was found between rs10511312、rs8636、rs362549、rs362998 and ADHD.Conclusion: The association study did find association between rs3746544 and ADHD which the meta-analysis also supported. However, this association is also need to be verified by subsequent functional studies.