biostudies-literatureUnknown31(8)Ansari MA<h4>Background</h4>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors. This study examined the specific gene variants, dopamine transporter 1 (DAT1) rs6350, dopamine receptor D3 (DRD3) rs6280, dopamine receptor D2 (DRD2) rs6277, and catechol-O-methyltransferase (COMT) rs4633, in relation to ADHD among Pakistani children by exploring the potential gene-gene and gene-environment interactions.<h4>Methods</h4>A total of 100 cases of ADHD and 100 healthy children were recruited. The tetra-primer amplification refractory mutation system (ARMS) assays were designed for genotyping the selected variants in both groups, and their association with ADHD was determined in different genetic models. Gene-gene and gene-environmental interactions were determined by the multifactor dimensionality reduction (MDR) method.<h4>Results</h4>The DAT1 rs6350 SNV AA genotype showed a significantly increased risk for ADHD in the codominant and recessive models. Conversely, the AG genotype demonstrated a protective factor for ADHD in the codominant and overdominant models. The DRD3 rs6280 T allele exhibited a decreased risk for ADHD, and the TT genotype showed a reduced risk in the recessive and log-additive models. No association between the DRD2 rs6277 and COMT rs4633 SNVs with ADHD was found in our population. The MDR analysis of the best three-fold interaction model showed redundancy between DAT1 rs6350 and DRD3 rs6280; however, the risk was increased with the gender variable, which showed a weak synergistic interaction with these SNVs.<h4>Conclusion</h4>Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.Saudi journal of biological sciences104045https://www.ebi.ac.uk/biostudies/studies/S-EPMC11268355biostudies-literatureGene-gene and gene-environmental interaction of dopaminergic system genes in Pakistani children with attention deficit hyperactivity disorder.PMC11268355Khidri FFNaqvi HAMahmood ARajput AHAnsari MAWaryah AMfalseGene-gene and gene-environmental interaction of dopaminergic system genes in Pakistani children with attention deficit hyperactivity disorder.<h4>Background</h4>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors. This study examined the specific gene variants, dopamine transporter 1 (DAT1) rs6350, dopamine receptor D3 (DRD3) rs6280, dopamine receptor D2 (DRD2) rs6277, and catechol-O-methyltransferase (COMT) rs4633, in relation to ADHD among Pakistani children by exploring the potential gene-gene and gene-environment interactions.<h4>Methods</h4>A total of 100 cases of ADHD and 100 healthy children were recruited. The tetra-primer amplification refractory mutation system (ARMS) assays were designed for genotyping the selected variants in both groups, and their association with ADHD was determined in different genetic models. Gene-gene and gene-environmental interactions were determined by the multifactor dimensionality reduction (MDR) method.<h4>Results</h4>The DAT1 rs6350 SNV AA genotype showed a significantly increased risk for ADHD in the codominant and recessive models. Conversely, the AG genotype demonstrated a protective factor for ADHD in the codominant and overdominant models. The DRD3 rs6280 T allele exhibited a decreased risk for ADHD, and the TT genotype showed a reduced risk in the recessive and log-additive models. No association between the DRD2 rs6277 and COMT rs4633 SNVs with ADHD was found in our population. The MDR analysis of the best three-fold interaction model showed redundancy between DAT1 rs6350 and DRD3 rs6280; however, the risk was increased with the gender variable, which showed a weak synergistic interaction with these SNVs.<h4>Conclusion</h4>Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.2024-01-01T00:00:00Z2024 Aug2026-06-01T09:02:28.996Z2026-04-08T11:04:59.43ZS-EPMC112683553905056010.1016/j.sjbs.2024.104045