Association between homozygosity of a G allele of the alpha-2a-adrenergic receptor gene and methylphenidate response in Korean children and adolescents with attention-deficit/hyperactivity disorder.
BACKGROUND
Methylphenidate (MPH) blocks the norepinephrine transporter as well as the dopamine transporter. The alpha-2a-adrenergic receptor is a key component of the noradrenergic system. The aim of this study was to evaluate the association between the ADRA2A -1291 C>G polymorphism and the response to MPH treatment in Korean subjects with attention-deficit/hyperactivity disorder (ADHD).


METHODS
This study enrolled 114 ADHD children (mean age = 9.08 +/- 1.94 years) from a child psychiatric clinic in South Korea. Subjects who had an improvement of >/= 50% compared with the baseline ADHD rating scale (ARS) score or who had a Clinical Global Impression-improvement score of 1 or 2 points after treatment were defined as the "good response". We examined the relationship of the ADRA2A to MPH response.


RESULTS
We found that a good response to MPH treatment, measured by the ARS as assessed by the parents, was observed for 76.9% of the subjects carrying the G/G genotype but for only 46.0% and 41.7% of those with the C/G and C/C genotypes, respectively [chi(2)(2) = 11.929, p = .003]. We also found a significant difference in the change in total ARS scores between subjects with and without the G/G genotype [t(1) = 2.21, p = .029].


CONCLUSIONS
Our findings provide evidence of an association between the ADRA2A -1291 C>G genotype and response to MPH treatment in Korean subjects with ADHD. Nonetheless, the methodological limitation of not being a randomized placebo-controlled trial and primarily basing results on parent report to clinicians suggest that these results should be viewed as more preliminary.
Cheon
Keun-Ah
KA
Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea. kacheon@dreamwiz.com
Cho
Dae-Yeon
DY
Koo
Min-Seong
MS
Song
Dong-Ho
DH
Namkoong
Kee
K
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006720:Homozygote; D006801:Humans; D007723:Korea; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*
C547768:ADRA2A protein, human; D000697:Central Nervous System Stimulants; D018341:Receptors, Adrenergic, alpha-2; D008774:Methylphenidate