The Association Between Dopamine Receptor Family Genetic Variation And Childhood Attention Deficit Hyperactivity Disorder

ObjectiveSystematically analyze the association between dopamine receptor family(DRD1-DRD5) genetic variation and susceptibility of childhood attention deficithyperactivity disorder.MethodsGenetic association studies containing case-control and family-based studies thatanalyzed polymorphisms in the DRD1, DRD2, DRD3, DRD4and DRD5genes withchildhood attention deficit hyperactivity disorder were identified via searches of theCBMdisc, PubMed, EMBASE and Google Scholar database prior to January2012.The meta-analysis procedures were performed using the metafor-package in R(version2.14.0) with random-effects models to estimate the pooled odds ratios (ORs).Some advanced analysis also ran in the R statistical platform to estimate the publishbias via Begg’s and Egger’s test, and analyze the source of heterogeneity, such asmeta-regression, sensitivity analysis, cumulative meta-analysis.ResultsThe results of present meta-analysis from68studies show that DRD5gene136bp (OR=0.58,95%CI=0.35-0.96),148bp (OR=1.26,95%CI=1.08-1.47) and shortallele (OR=0.81,95%CI=0.67-0.98), DRD2gene TaqI ’A1’ allele (OR=1.65,95%CI=1.05-2.58), DRD4gene4-repeat (OR=0.92,95%CI=0.85-0.997),7-repeat(OR=1.35,95%CI=1.20-1.51), short (OR=0.83,95%CI=0.73-0.94) and long allele(OR=1.28,95%CI=1.10-0.48) all significantly associated with attention deficit hyperactivity disorder, while the others have no relation with the disorder. Moreover,we detect ethnicity, publish year and study method could explain the heterogeneousacross studies in meta-regression during evaluation of the results in meta-analysis andthe study of DRD45-repeat exist publish bias.ConclusionThe DRD5，DRD2and DRD4gene of the dopamine receptor family associatedwith the childhood attention deficit hyperactivity disorder, thus providing quantitativeepidemiology evidence for understanding the pathogenesis of this disease. Race,publish year and study method are the usual heterogeneity source, thus providingdirection for explaining the heterogeneity.