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


ABSTRACT:

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.

SUBMITTER: Ansari MA 

PROVIDER: S-EPMC11268355 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Ansari Moin Ahmed MA   Naqvi Habib Ahmed HA   Khidri Feriha Fatima FF   Rajput Aatir Hanif AH   Mahmood Ambar A   Waryah Ali Muhammad AM  

Saudi journal of biological sciences 20240621 8


<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 10  ...[more]

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