The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD
Background and Objectives: Most genetic studies have focused on catecholamine system genes to identify etiology in attention-deficit/hyperactivity disorder (ADHD), and there is growing evidence that the interaction of several genes may synergistically or antagonistically affect disease outcomes. We...
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MDPI AG
2025-05-01
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| author | Jewook Kang Bum-Sung Choi Bongseog Kim |
| author_facet | Jewook Kang Bum-Sung Choi Bongseog Kim |
| author_sort | Jewook Kang |
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| description | Background and Objectives: Most genetic studies have focused on catecholamine system genes to identify etiology in attention-deficit/hyperactivity disorder (ADHD), and there is growing evidence that the interaction of several genes may synergistically or antagonistically affect disease outcomes. We investigated the interaction between the alpha-2 adrenergic receptor (<i>ADRA2A</i>) and its transporter (<i>SLC6A2</i>) to determine the etiology and treatment outcomes for ADHD. Materials and Methods: Children with ADHD (age 8.3 ± 2.0 y, 72 boys and 11 girls) were assessed using the Kiddie Schedule for Affective Disorders-Present and Lifetime (K-SASD-PL), ADHD rating scale-IV (ARS), Clinical Global Impressions-Improvement (CGI-I), and Clinical Global Impressions-Severity (CGI-S) scales. Neuropsychological assessments were performed using a continuous performance test (CPT). Methylphenidate was titrated based on the CGI-I and CGI-S scales for 8 weeks. We assessed two polymorphisms, <i>ADRA2A</i> rs553668 and <i>SLC6A2</i> rs998424, for their association with disease outcomes. Results: The <i>ADRA2A</i> polymorphism had a significant effect on visual/auditory commission errors in the CPT. The CC genotype for <i>ADRA2A</i> combined with the GG genotype for <i>SLC6A2</i> showed more commission errors than the other combinations of genotypes. Treatment outcome assessment using the CGI-S showed that the <i>SLC6A2</i> GG genotype had more favorable treatment outcome (<i>p</i> < 0.05) and significant gene × dose interaction on ARS score across 8 weeks (<i>p</i> < 0.01). Conclusions: Our findings provide preliminary evidence for the effect of <i>ADR2A</i> and <i>SLC6A2</i> gene–gene interactions on the attention system and treatment response in children with ADHD. Although these findings require future replication, our study contributes to the understanding of the genetic basis of ADHD. |
| format | Article |
| id | doaj-art-d86ed5e44137459daa214ae412d05cda |
| institution | Kabale University |
| issn | 2227-9067 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Children |
| spelling | doaj-art-d86ed5e44137459daa214ae412d05cda2025-08-20T03:27:29ZengMDPI AGChildren2227-90672025-05-0112670410.3390/children12060704The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHDJewook Kang0Bum-Sung Choi1Bongseog Kim2Department of Psychiatry, Inje University Pusan Paik Hospital, Inje University College of Medicine, Pusan 47392, Republic of KoreaDepartment of Psychiatry, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Psychiatry, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul 01757, Republic of KoreaBackground and Objectives: Most genetic studies have focused on catecholamine system genes to identify etiology in attention-deficit/hyperactivity disorder (ADHD), and there is growing evidence that the interaction of several genes may synergistically or antagonistically affect disease outcomes. We investigated the interaction between the alpha-2 adrenergic receptor (<i>ADRA2A</i>) and its transporter (<i>SLC6A2</i>) to determine the etiology and treatment outcomes for ADHD. Materials and Methods: Children with ADHD (age 8.3 ± 2.0 y, 72 boys and 11 girls) were assessed using the Kiddie Schedule for Affective Disorders-Present and Lifetime (K-SASD-PL), ADHD rating scale-IV (ARS), Clinical Global Impressions-Improvement (CGI-I), and Clinical Global Impressions-Severity (CGI-S) scales. Neuropsychological assessments were performed using a continuous performance test (CPT). Methylphenidate was titrated based on the CGI-I and CGI-S scales for 8 weeks. We assessed two polymorphisms, <i>ADRA2A</i> rs553668 and <i>SLC6A2</i> rs998424, for their association with disease outcomes. Results: The <i>ADRA2A</i> polymorphism had a significant effect on visual/auditory commission errors in the CPT. The CC genotype for <i>ADRA2A</i> combined with the GG genotype for <i>SLC6A2</i> showed more commission errors than the other combinations of genotypes. Treatment outcome assessment using the CGI-S showed that the <i>SLC6A2</i> GG genotype had more favorable treatment outcome (<i>p</i> < 0.05) and significant gene × dose interaction on ARS score across 8 weeks (<i>p</i> < 0.01). Conclusions: Our findings provide preliminary evidence for the effect of <i>ADR2A</i> and <i>SLC6A2</i> gene–gene interactions on the attention system and treatment response in children with ADHD. Although these findings require future replication, our study contributes to the understanding of the genetic basis of ADHD.https://www.mdpi.com/2227-9067/12/6/704ADHD<i>ADRA2A</i><i>SLC6A2</i>CPTtreatment outcomegene–gene interaction |
| spellingShingle | Jewook Kang Bum-Sung Choi Bongseog Kim The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD Children ADHD <i>ADRA2A</i> <i>SLC6A2</i> CPT treatment outcome gene–gene interaction |
| title | The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD |
| title_full | The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD |
| title_fullStr | The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD |
| title_full_unstemmed | The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD |
| title_short | The Role of Gene–Gene Interaction Between <i>ADRA2A</i> and <i>SLC6A2</i> Polymorphisms in Attention System and Treatment Outcomes for Children with ADHD |
| title_sort | role of gene gene interaction between i adra2a i and i slc6a2 i polymorphisms in attention system and treatment outcomes for children with adhd |
| topic | ADHD <i>ADRA2A</i> <i>SLC6A2</i> CPT treatment outcome gene–gene interaction |
| url | https://www.mdpi.com/2227-9067/12/6/704 |
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