attention deficit hyperactivity disorder (ADHD) dopamine dopa decarboxylase association haplotype based haplotype relative risk (HHRR)
Nature Publishing Group
Z. Hawi, D. Foley, A. Kirley, M. McCarron, M. Fitzgerald and M. Gill, Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity disorder (ADHD): no evidence for association in the Irish population, Molecular psychiatry, 6, 4, 2001, 420-424
Molecular psychiatry 6 4
Dopa decarboxylase (DDC) is an enzyme which catalyses the decarboxylation of both dopa to dopamine and L-5 hydroxytryptophan to serotonin. Both catecholamines are major neurotransmitters of the mammalian nervous system. It has been suggested that genes involved in the dopaminergic system play a primary role in predisposing to attention deficit hyperactivity disorder (ADHD). In this study, the 4-bp insertion/deletion variant mapped to the first neuronally expressed exon 1 at the dopa decarboxylase gene and two microsatellite markers flanking the gene were investigated for possible association with ADHD. Using HHRR, we observed an increased transmission (though not significant) of the 4-bp insertion (allele 1) to ADHD cases (chi2 = 2.72, P = 0.1, RR = 1.25). However marginally significant excess transmission of allele 10 (213 bp) of the 3' microsatellite D7S2422 (~0.75 cM distal to dopa decarboxylase gene) was found (chi2 = 4.2, P = 0.04, RR=1.48). Interestingly, a haplotype containing both alleles is transmitted more frequently (chi2= 5, P = 0.025). Analysing data by the sex of transmitting parent showed a greater relative risk for paternal transmission of the 4-bp insertion allele and allele 10 of the D7S2422 (RR = 1.48 and 1.63 respectively). This provides preliminary evidence that this locus or a closely mapped DNA variant may be involved in the genetic susceptibility to ADHD. However, further studies are required to either confirm or refute these observations.
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