Dopamine D2 receptor gene polymorphisms and externalizing behaviors in children and adolescents

Abstract

BackgroundDopamine is involved in several cerebral physiological processes, and single nucleotide polymorphisms (SNP) in the dopamine D2 receptor gene (DRD2) have been associated with numerous neurological and mental disorders, including those involving alterations in cognitive and emotional processes.MethodsThe aim of this study was to evaluate the association between the SNPs c.957C > T (rs6277) and c.-585A > G (rs1799978) in the DRD2 gene and behavioral characteristics of children and adolescents based on an inventory of the Child Behavior Checklist (CBCL). Children and adolescents between 8 and 20 years old who were clinically followed-up were genotyped for the SNPs c.957C > T and c.-585A > G, and related to data of the CBCL/6–18 scale assessment performed with the help of caregivers. The chi-squared test was used to assess the differences in the frequencies of the C and T alleles in the polymorphism c.957C > T and of the A and G alleles in the polymorphism c.-585A > G with respect to the grouped CBCL scores at a significance level of 5%. Multiple logistic regression models were performed, to control whether sex and/or ethnicity could influence the results.ResultsEighty-five patients were assessed overall, and the presence of the T allele (C/T and T/T) of DRD2 c.957C > T polymorphism was found to be significantly associated with the occurrence of defiant and oppositional problems and with attention and hyperactivity problems. There were no associations detected with polymorphism DRD2 c.-585A > G polymorphism. Both SNPs were in Hardy-Weinberg-equilibrium.ConclusionsAlthough the findings of this study are preliminary, due to its small number of participants, the presence of T allele (C/T, T/T) in c.957C > T SNP was associated with difficulty in impulse control, self-control of emotions, and conduct adjustment, which can contribute to improving the identification of mental and behavioral phenotypes associated with gene expression.

Gene-gene and gene-environmental interaction of dopaminergic system genes in Pakistani children with attention deficit hyperactivity disorder

“…The synonymous SNV rs6277T allele (957C > T; Pro319Pro) has shown a reduction in translation and mRNA stability, resulting in a decrease of up to 50 % in protein synthesis compared to the C allele. Furthermore, a significant association has been found between the T allele and genotypes CT and TT with defiant and oppositional problems, attention and hyperactivity ( Della Torre et al, 2018 ). In contrast to these findings, our study suggests no association between rs6277 and ADHD in Pakistani children.…”

Prenatal metals exposure and pre-adolescents’ emotional and behavioral problems

“…Some single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE), Brain Derived Neurotrophic Factor (BDNF), Glutathione S-Transferase Pi 1 (GSTP1) and Paraoxonase 1 (PON1) genes, have shown a possible role in pathways related with metal neurotoxicity (Gaynor et al 2009;Benke et al 2014;Trucco et al 2018;Della Torre et al 2018;Paes et al 2018;Cimino et al 2020;Lozano et al 2021;Treble-Barna et al 2022). For instance, a Taiwanese study (Ng et al 2015) observed that children's carriers of APOE ε4 showed a higher risk of internalizing and externalizing problems with increasing mercury at the age of two years.…”

A systematic review and meta-analyses of the relationship between glutathione S-transferase gene polymorphisms and renal cell carcinoma susceptibility

“…But, the current evidence is inadequate, for the reason that sparseness of data or inconsistencies among these reported investigations. This meta-analysis was conducted to assess whether the null genotype of GSTM1/GSTT1 and the GSTP1 A/G gene polymorphism are associated with RCC susceptibility by ethnicity, and whether there is an association between the null genotype of GSTM1/GSTT1 and clinical TNM stages in patients with RCC by ethnicity, due to the fact that the genotype distributions of the different populations might differ from each other [ 27 , 28 ]. We also evaluated the publication bias for the relationship between the GSTM1 -null genotype, GSTT1 -null genotype, dual GSTM1/GSTT1 -null genotype, and GSTP1 A/G gene polymorphism and RCC risk for the overall population.…”