High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sibpairs with ADHD.
BACKGROUND
A minority of patients with attention-deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4) 7-repeat alleles. This study examined the sibling correlation of methylphenidate response rate and the possible association between response rate and these risk alleles.


METHODS
A sample of 82 Dutch children with ADHD, from 54 families, (including 30 singletons and 28 sib pairs), who used methylphenidate, was phenotyped according to DSM-IV criteria. Patients were members of affected sib pairs and were genotyped for DAT1 and DRD4. The sibling Intraclass Correlation Coefficient for methylphenidate response rate was calculated. The association between individual response rates and the risk alleles was examined using linear regression techniques.


RESULTS
The Intraclass Correlation Coefficient was significant (r=.563, p=.001). No evidence was found establishing an association between methylphenidate response and DAT1-homozygosity. There was a positive trend towards association with the presence of one or two DRD4-7R alleles.


CONCLUSIONS
The sibling correlation may indicate a familial clustering of methylphenidate response. This response is possibly associated with the presence of one or two alleles at the DRD4-7R locus, but not with DAT1-10R homozygosity in the Dutch population.
van der Meulen
Emma M
EM
Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Evandermeulen_2000@yahoo.com
Bakker
Steven C
SC
Pauls
David L
DL
Oteman
Nicole
N
Kruitwagen
Cas L J J
CL
Pearson
Peter L
PL
Sinke
Richard J
RJ
Buitelaar
Jan K
JK
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D015897:Comorbidity; D015259:Dopamine Agents / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology; D008774:Methylphenidate / Q000494:pharmacology*; D018598:Minisatellite Repeats; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012044:Regression Analysis; D012189:Retrospective Studies; D012306:Risk; D035781:Siblings
C493599:DRD4 protein, human; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D008774:Methylphenidate