Association Of NTRK2,DRD4 And Other Gene Polymorphisms With Attention-Deficit/Hyperactivity Disorder In Children

Objective: To identify the types and frequencies of base mutations of single nucleotide polymorphism(SNP)sites of NTRK2,DRD4 and others,and to explore the association of their polymorphisms with attention-deficit/hyperactivity disorder(ADHD)and subtypes of ADHD in children,so as to provide theoretical basis for the research on genetic susceptibility of ADHD.Methods: A case-control study design was adopted,212 ADHD children who were treated in Wuhan children’s hospital,and 265 healthy children from an elementary school,were totally surveyed.Self-made questionnaire was used to collect children’s demographic characteristics,birth related history,behavioral and family information;Vanderbilt parents rating scale was used to evaluate the symptoms of ADHD,ADHD is divided into predominantly inattentive subtype(ADHD-I)and predominantly hyperactivity/impulsivity and combined subtype(ADHD-HI/C).Venous blood samples of children were collected at the same time.The SNP sites of NTRK2、DRD4、DAT1、SLC6A2 and HTR1 B were detected and classified.The risk factors of ADHD were screened out by calculating odd ratio(OR)and 95% confidence interval(CI)with t/chi square test and logistic regression equation.Results: Adjusted for confounding factors,children who carried NTRK2 rs10780691 CT genotype had a 61% lower risk of ADHD(OR=0.39,95%CI: 0.17-0.91)compared with children with CC genotype.Under the dominant model,the risk of ADHD and ADHD-HI/C in children with NTRK2 rs10780691 CT/TT genotype reduced by 63%(OR=0.37,95%CI: 0.16-0.81)and 69%(OR=0.31,95%CI: 0.10-0.95)than that in children with CC genotype,respectively.In addition,under the additive model,the risk of ADHD,ADHD-I and ADHD-HI/C for children decreased significantly with each additional T allele at NTRK2 rs10780691.For DRD4 rs3758653,children who had CT genotype had 3.02 times risk of ADHD than children carried TT genotype(OR=3.02,95%CI: 1.29-7.05).In dominant model,the risk of ADHD and ADHD-HI/C for children with CC/CT genotype was 1.81 times higher(OR=2.81,95%CI:1.25-6.34)and 2.23 times higher(OR=3.23,95%CI:1.04-10.01)compared with children who carried DRD4 rs3758653 TT genotype,respectively.Besides,in the additive model,for each additional C allele at this locus,the prevalence of ADHD increased by 73%(OR=1.73,95%CI: 1.01-2.96).The cumulative effect analysis showed that children with NTRK2 rs10780691 CC and DRD4 rs3758653 CC/CT risk genotypes had a 5.28 times higher risk of ADHD than non-carriers(OR=6.28,95%CI: 1.86-13.47),but the linear trend test of chi square showed that the risk of ADHD in children had no linear trend correlation with the number of risk genotypes studied.The polymorphisms of DAT1 rs27048,NET rs2242447 and HTR1 B rs6296 were not statistically associated with ADHD in children.Conclusions: NTRK2 rs10780691 and DRD4 rs3758653 polymorphisms are significantly related with ADHD and subtypes of ADHD in children,providing scientific clues for the future research on the genetic susceptibility of ADHD in children;There are differences between symptom subtypes of ADHD in terms of the genetic susceptibility,so the pathogenic mechanism of ADHD among children should be explored according to the sub-symptoms’ classification of ADHD.