Abstract
BackgroundAttention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity. Molecular genetic and pharmacological studies suggest the involvement of the dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine oxidase A (MAO-A) encodes an enzyme that degrades biogenic amines, including neurotransmitters such as norepinephrine, dopamine and serotonin. In this study we examined a 30 bp promoter variable number tandem repeat (VNTR) and a functional G/T single nucleotide polymorphism (SNP) at position 941 in exon 8 (941G/T) of MAO-A for association with ADHD in a Taiwanese sample of 212 ADHD probands.MethodsWithin-family transmission disequilibrium test (TDT) was used to analyse association of MAO-A polymorphisms with ADHD in a Taiwanese population.ResultsA nominally significant association was found between the G-allele of 941G/T in MAO-A and ADHD (TDT: P = 0.034. OR = 1.57). Haplotype analysis identified increased transmission of a haplotype consisting of the 3-repeat allele of the promoter VNTR and the G-allele of the 941G/T SNP (P = 0.045) to ADHD cases which the strong association with the G-allele drove.ConclusionThese findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD in the Taiwanese population. These results replicate previously published findings in a Caucasian sample.
Highlights
Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity
We looked at 4% of the ADHD cases which showed oppositional defiant disorder in our samples
The results revealed that the 4% cases did not drive the nominal association
Summary
Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity. Monoamine oxidase A (MAO-A) encodes an enzyme that degrades biogenic amines, including neurotransmitters such as norepinephrine, dopamine and serotonin. Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioural disorders characterised by inattention, hyperactivity and impulsivity. Polymorphic variants in several genes involved in regulation of the dopamine, and related neurotransmitter pathways are reported to be associated with ADHD [2,3]. MAO-A degrades biogenic amines such as dopamine and serotonin, providing control of the level of these neurotransmitters in the central nervous system. MAO-A knockout mice have elevated brain levels of serotonin, norepinephrine and dopamine and manifest aggressive behaviour [4]. Caspi et al [5] reported that maltreated children with a genotype conferring high levels of MAO-A expression were less likely to develop antisocial problems
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