American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Apr 2009
Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults.
It has been suggested that symptoms of attention-deficit/hyperactivity disorder (ADHD) is related to low dopamine levels in the prefrontal cortex. The enzyme catechol O-methyltransferase (COMT), which degrades dopamine and other catecholamines, is important for monoamine signaling in this brain-region, but genetic studies of the functional Val158Met (rs4680) polymorphism in ADHD have been inconsistent. However, recently it was shown that also common synonymous COMT variants modulate total COMT enzymatic activity by affecting the expression of the gene [Nackley et al. (2006); Science 314(5807):1930-1933]. ⋯ Haplotype analysis revealed that the rs6269 risk allele tags the suggested high COMT-activity haplotype, which is associated with the highest hyperactivity/impulsivity score in our sample (P = 0.01). Our results also suggest that there is a stepwise decreased hyperactivity/impulsivity score associated with the proposed mid and low activity haplotypes described previously. In conclusion, we suggest that COMT haplotype variation is associated primarily with the hyperactivity/impulsivity dimension of ADHD and point to the importance of testing this hypothesis in future studies.