The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.

Expression of alpha 2A -adrenergic receptor mRNA in the dorsal root ganglia in a rat neuropathic pain model / 체질인류학회지

To investigate whether the change of alpha 2A -AR mRNA expression in the DRG is an underlying mechanism of sympathetically maintained neuropathic pain (SMP), in situ hybridization for alpha 2A -adrenergic receptor (AR) mRNA with digoxigenin -labeled RNA probe in the rat DRG was conducted after tight ligation of the 5th lumbar (L5) spinal nerve up to 12 weeks. Majority of the DRG neurons expressed alpha 2A -AR mRNA and a few satellite cells expressed alpha 2A -AR mRNA in the DRG of the contralateral side. The number of the alpha 2A -AR mRNA positive DRG neurons dropped significantly at 7 day post -operation (7D PO). On the other hand, there was great increase in the number of the alpha 2A -AR positive satellite cells at 7D PO. Then, the number of the alpha 2A -AR mRNA positive DRG neurons was increased and the number of the alpha 2A -AR mRNA positive satellite cells was decreased from 7D PO to 12 weeks PO. Surgical sympathectomy reduced neuropathic pain behaviors in animal models of neuropathic pain suggest that downregulation of alpha 2A -AR mRNA expression in the injured DRG neurons following the ligation itself might be not related to SMP, but the role of upregulation of alpha 2A -AR mRNA expression in the satellite cells remain to be explored.