Gene-gene interaction between COMT and MAOA potentially predicts the intelligence of attention-deficit hyperactivity disorder boys in China.
The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism (Val158Met) affecting the activity of the enzyme, and the monoamine oxidase A (MAOA) gene contains a VNTR polymorphism (MAOA-uVNTR) that affects the transcription of the gene. COMT and MAOA each contribute to the enzymatic degradation of dopamine and noradrenaline. Prefrontal cortical (PFC) function, which plays an important role in individual cognitive abilities, including intelligence, is modulated by dopamine. Since our previous association studies between attention deficit hyperactivity disorder (ADHD) and these two functional polymorphisms consistently showed the low activity alleles were preferentially transmitted to inattentive ADHD boys, the goal of the present study was to test the hypothesis that the interaction between COMT Val158Met and MAOA-uVNTR may affect the intelligence in a clinical sample of Chinese male ADHD subjects (n = 264). We found that the COMT x MAOA interaction significantly predicted full scale (FSIQ) and performance (PIQ) IQ scores (P = 0.039, 0.011); the MAOA-uVNTR significantly predicted FSIQ, PIQ and verbal IQ (VIQ) (P = 0.009, 0.019, 0.038); COMT Val158Met independently had no effect on any of the IQ scores. Only the COMT x MAOA interaction for PIQ remained significant after a Bonferroni correction. Among all combined genotypes, the valval-3R genotype predicted higher intelligence, (average 106.7 +/- 1.6, 95% C.I. 103.7-109.8 for FSIQ), and the valval-4R predicted lower intelligence (average 98.0 +/- 2.3, 95% C.I. 93.5-102.6 for FSIQ). These results suggest that there is an inverted U-shaped relationship between intelligence and dopaminergic activity in our sample. Our finding that gene-gene interaction between COMT and MAOA predicts the intelligence of ADHD boys in China is intriguing but requires replication in other samples.
Qian
Qiu-Jin
QJ
Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, 100191, Beijing, China.
Yang
Li
L
Wang
Yu-Feng
YF
Zhang
Hao-Bo
HB
Guan
Li-Li
LL
Chen
Yun
Y
Ji
Ning
N
Liu
Lu
L
Faraone
S V
SV
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000208:ethnology* / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002681:China; D004298:Dopamine / Q000378:metabolism; D004843:Epistasis, Genetic; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic
D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine