Gene–Gene Interaction Between COMT and MAOA Potentially Predicts the Intelligence of Attention-Deficit Hyperactivity Disorder Boys in China

Abstract

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.

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The current status of research into attention deficit hyperactivity disorder: proceedings of the 2nd international congress on ADHD: from childhood to adult disease

“…Possibly, there is some association between ADHD and polymorphisms of genes involved in the dopaminergic neurotransmitter system such as DRD4, DRD5, DAT, COMT and MAOA. Recently identified possible candidate genes include CDH13, SLC9A9 and LPHN3 as well as ASTN2, DIRAS2, CTNNA2, KALRN, NOS1, GIRK2 and CNR1 (Asherson 2009;Franke 2009;Jacob et al 2009;Leung et al 2009;Renner et al 2009;Qian et al 2009;Weißflog et al 2009). A variant of the latrophilin 3 gene (LPHN3), possibly together with other polymorphisms, could predict treatment outcome (Deckert 2009;Muenke 2009).…”