Possible association of the alpha-2A-adrenergic receptor gene with response time variability in attention deficit hyperactivity disorder.
Previous studies have demonstrated that the MspI and DraI polymorphisms at the alpha-2A-adrenergic receptor gene (ADRA2A) are associated with ADHD. However, few studies have been designed to ascertain the association between the ADRA2A genotypes and the performance on neurocognitive measures in ADHD. The aims of this study were to examine the association of the ADRA2A MspI and DraI polymorphisms with ADHD in Korean subjects, and to determine the relationship between the genotypes of these two polymorphisms and the candidate endophenotypes, as measured by the continuous performance test (CPT). In a case-control study, we assessed 186 ADHD probands and 150 normal controls. One hundred eight trios were studied in a family based association analysis. The transmission disequilibrium test (TDT) analysis showed preferential transmission of the C allele of the DraI polymorphism (chi(2) = 5.88, P = 0.015). In the haplotype analyses, a trend of over-transmission of haplotype C/C was observed (chi(2) = 3.80, P = 0.051). The homozygous subjects for the C allele (C/C genotype) at the DraI polymorphism showed a trend toward a higher mean T-score with respect to the response time variability profiles of the CPT than did those with the other genotypes (C/T + T/T genotypes; P = 0.042). The homozygous subjects for the G allele (G/G genotype) at the MspI polymorphism showed a tendency to have a lower mean T-score with respect to the response time variability profiles of the CPT (P = 0.068). The results of this study provide important evidence for the involvement of the ADRA2A MspI and DraI polymorphisms in the etiology of ADHD in Korean subjects. In addition, our results provide evidence for the possible role of these two polymorphisms in ADHD symptom expression, such as increased response time variability.
Cho
Soo-Churl
SC
Department of Child and Adolescent Psychiatry, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Kim
Jae-Won
JW
Kim
Boong-Nyun
BN
Hwang
Jun-Won
JW
Park
Mira
M
Kim
Soon Ae
SA
Cho
Dae-Yeon
DY
Yoo
Hee-Jeong
HJ
Chung
Un-Sun
US
Son
Jung-Woo
JW
Park
Tae-Won
TW
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D016022:Case-Control Studies; D002648:Child; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011930:Reaction Time / Q000235:genetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*
C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; C035594:TTTAAA -specific type II deoxyribonucleases