Gene-gene and gene-environmental interaction of dopaminergic system genes in Pakistani children with attention deficit hyperactivity disorder.
PMID 39050560 | PMCID PMC11268355 | DOI 10.1016/j.sjbs.2024.104045 · Saudi journal of biological sciences · 2024 · View on PubMed ↗
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | DRD3 | “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.” | 0.98 | hgnc_dict_v1 |
| gene | DRD2 | “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.” | 0.98 | hgnc_dict_v1 |
| gene | COMT | “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.” | 0.98 | hgnc_dict_v1 |
| phenotype | neurodevelopmental disorder | “BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors.” | 0.98 | phenotype_alias_lexicon_v2 |
| variant | rs6350 | “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.” | 0.90 | hgvs_regex_v1 |
| variant | rs6280 | “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.” | 0.90 | hgvs_regex_v1 |
| variant | rs6277 | “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.” | 0.90 | hgvs_regex_v1 |
| variant | rs4633 | “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.” | 0.90 | hgvs_regex_v1 |