Genetic Association of HTR1B and HTR2A Gene Polymorphisms with ADHD in Korean Children and Adolescents: A Case
Yeongsuk Lee1,2, Hyung Jun Kim3, Han Jun Jin3
1Department of Psychiatry, Graduate School, Soonchunhyang University, Asan 31538, Republic of Korea.
Insights
Genetic variations in the HTR2A gene may influence attention-deficit hyperactivity disorder (ADHD) susceptibility. This study found a potential link between HTR2A rs9534495 and ADHD in a Korean sample, though further research is needed.
Area of Science:
- Neurogenetics
- Psychiatric Genetics
- Molecular Psychiatry
Background:
- Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder.
- Serotonergic system genes are implicated in ADHD pathophysiology.
- Investigating specific gene polymorphisms can elucidate ADHD genetic susceptibility.
Purpose of the Study:
- To examine the association between HTR1B and HTR2A gene polymorphisms and ADHD risk in a Korean population.
- To identify specific single nucleotide polymorphisms (SNPs) within the serotonergic pathway linked to ADHD.
- To understand the role of serotonergic system variations in ADHD development.
Main Methods:
- Case-control study involving 234 children with ADHD and 1686 healthy controls.
- Genotyping of HTR1B (rs6296) and HTR2A (rs6311, rs6313, rs9534495) SNPs.
- Statistical analysis using Chi-square tests and odds ratios across different inheritance models.
Main Results:
- A significant association was found between HTR2A rs9534495 and ADHD under dominant, recessive, and additive models (p < 0.05).
- These associations did not remain significant after Bonferroni correction.
- No significant associations were observed for HTR1B rs6296 or other HTR2A SNPs (rs6311, rs6313).
Conclusions:
- Genetic variations in the HTR2A gene may contribute to ADHD susceptibility.
- The study highlights potential roles of serotonergic genes in ADHD.
- Further large-scale, multi-ethnic studies with functional assays are recommended to confirm findings.
Objectives:
Attention-deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed during childhood, primarily characterized by continuous symptoms of inattention, hyperactivity, and impulsivity. The present study aimed to investigate the genetic association between polymorphisms in the serotonergic system-related genes, HTR1B and HTR2A, and the susceptibility to ADHD in a Korean sample.
Methods:
The study cohort consisted of 234 children diagnosed with ADHD and 1686 healthy controls. Clinical diagnosis was established based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Genetic analysis focused on single nucleotide polymorphisms (SNPs) within the serotonergic pathway: rs6296 in HTR1B, and three SNPs (rs6311, rs6313, and rs9534495) in HTR2A. Genotype and allele frequencies were analyzed using Chi-square tests. Risk estimates were calculated as odds ratios (OR) with 95% confidence intervals (CI) across dominant, recessive, and additive inheritance models.
Results:
A statistically significant association was observed between the HTR2A rs9534495 polymorphism and ADHD. Specifically, significant associations were identified under the dominant (OR 0.67, 95% CI 0.48-0.93, p = 0.017), recessive (OR 0.67, 95% CI 0.48-0.93, p = 0.016), and additive (OR 0.80, 95% CI 0.65-1.00, p = 0.046) models. However, these significant findings did not persist after applying the Bonferroni correction for multiple comparisons. Conversely, no significant associations were detected for the HTR1B (rs6296) and the other HTR2A (rs6311, rs6313) polymorphisms.
Conclusions:
These findings suggest that genetic variations in the serotonergic system, particularly within the HTR2A gene, may contribute to the genetic susceptibility to ADHD. This study confirmed gene SNIPs associated with the serotonergic system in the pathophysiology of ADHD. Future research involving large-scale multi-ethnic cohorts, functional assays, and gene-environment interaction analyses is warranted to further elucidate the underlying mechanisms of serotonergic genes.
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