Association Between BDNF Gene Polymorphism And Environmental Factors On Attention Deficit Hyperactivity Disorder In School-aged Children

Objective:To understand the characteristics of attention deficit hyperactivity disorder and exposure levels of phthalate esters（PAEs）metabolite in school-aged children in Wuhan.To understand functional role of brain-derived neurotrophic factor（BDNF）.To explore the association between BDNF gene polymorphism,PAEs metabolite exposure level,and their interactions with ADHD in children,to explore risk factors of ADHD,and to provide theoretical basis for scientific prevention.Methods:A case-control study was applied in this study.The ADHD cases were collected in two hospitals during May 2017 and December 2018 in Wuhan.The healthy controls were collected in a primary school according to the inclusion criterion of control in the study.Self-made children’s health interview questionnaire was used to collect the characteristics of participants,family and environmal factors.The NICHQ Vanderbilt ADHD Diagnostic Parental Rating Scale was used to assess ADHD symptoms.With informed consent of paticipants’parents,children’s urine and blood samples were collected.The concentration of PAEs metabolite in urine was detected by LC-MS;the polymorphism of BDNF gene in blood was detected by im LDR^TMtechnique.The chi-square test and logistic regression model were used for univariate analysis.The additive interaction model and the multiplicative interaction model in logistic regression were used to identify risks of gene-environment interactions.Results:1.Children with genotype AA or CA in rs10835210 exhibited increased risk of ADHD（OR=6.98,95%CI:1.51-32.31）compared with genotype CC children.2.PAEs metabolite exposure level showed that MMP（OR=4.26,95%CI:1.60-11.31）,MEHHP（OR=5.15,95%CI:1.91-13.91）,MBP（OR=2.84,95%CI:1.13-7.20）,MEOHP（OR=7.52,95%CI:2.27-24.97）,MEHP（OR=7.43,95%CI:2.25-24.57）exposures are associated with a high prevelance risk of ADHD.3.The results of gene-environment interaction showed that:（1）There was a significant multiplicative interaction between rs6265 and MBZP exposure level（P<0.05）,and there was a significant additive interaction between rs6265 and MBP exposure level（AP=0.82,95%CI:0.30-1.35）.（2）There was a significant additive interaction between rs7103411 and MBP exposure level（AP=0.83,95%CI:0.31-1.36）.（3）There was a significant additive interaction between rs10835210 and MEP exposure level（AP=0.85,95%CI:0.55-1.15）.All the above interactions are significantly related to ADHD.Conclusion:Allelic mutation at rs10835210 may increase risk of ADHD in children.High exposures to phthalate metabolites MMP,MEHHP,MBP,MEOHP and MEHP are associated with higher likelihood of ADHD,and these may be risk factors for the occurrence of ADHD.There are multiplicative or additive interactions between rs6265,rs7103411,rs10835210 and PAEs metabolite exposure,suggesting that BDNF gene-environment interaction may influence the risk of ADHD.