title: Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity disorder (ADHD): no evidence for association in the Irish population.
abstract: 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 (chi(2) = 2.72, P = 0.1, RR = 1.25). However marginally significant excess transmission of allele 10 (213 bp) of the 3' microsatellite D7S2422 ( approximately 0.75 cM distal to dopa decarboxylase gene) was found (chi(2) = 4.2, P = 0.04, RR=1.48). Interestingly, a haplotype containing both alleles is transmitted more frequently (chi(2)= 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.
authors.affiliation: Department of Genetics, Trinity College, Dublin 2, Ireland. zhhawi@tcd.ie
authors.forename: Z
authors.initials: Z
authors.lastname: Hawi
authors.forename: D
authors.initials: D
authors.lastname: Foley
authors.forename: A
authors.initials: A
authors.lastname: Kirley
authors.forename: M
authors.initials: M
authors.lastname: McCarron
authors.forename: M
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: M
authors.initials: M
authors.lastname: Gill
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D004247:DNA / Q000097:blood; D004251:DNA Transposable Elements; D004296:Dopa Decarboxylase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007494:Ireland; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D044465:White People
chemical_list: D004251:DNA Transposable Elements; D004247:DNA; D004296:Dopa Decarboxylase