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

• Published in: Saudi journal of biological sciences Vol. 31; no. 8; p. 104045
• Main Authors: Ansari, Moin Ahmed, Naqvi, Habib Ahmed, Khidri, Feriha Fatima, Rajput, Aatir Hanif, Mahmood, Ambar, Waryah, Ali Muhammad
• Format: Journal Article
• Language: English
• Published: Saudi Arabia Elsevier B.V 01-08-2024; Elsevier
• Subjects: ADHD; Environment; Gene; Interaction; Original; Variant; Variant; ADHD; Environment; Gene; Interaction
• ISSN: 1319-562X; 2213-7106
• DOI: 10.1016/j.sjbs.2024.104045

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.
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.
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.
Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.