Investigation of dopamine receptor (DRD4) and dopamine transporter (DAT) polymorphisms for genetic linkage or association to panic disorder

Clinical and animal studies suggest a role for the neurotransmitter dopamin e in anxiety states. In humans, one such condition is panic disorder, which is typified by recurrent panic attacks accompanied by anticipatory anxiety . Family, segregation, and twin studies imply a genetic component to the pa thophysiology of panic disorder. In this study, we examined the genes for t he D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) using thr ee common sequence polymorphisms, Two of these polymorphisms were in DRD4, a 12 basepair insertion/deletion in exon 1 and a 48 base-pair repeat in exo n 3, and the third was a 40 base-pair repeat in the 3' untranslated region of DAT. We employed a family-based design, using 622 individuals in 70 fami lies, as well as 82 haplotype relative risk "trios", Subjects were genotype d at the polymorphic loci, and the data were analyzed for genetic associati on and linkage. There were no significant differences in allele frequencies or occurrence of genotypes within the triads for any of the three polymorp hisms. No significant linkage between the DRD4 or DAT polymorphisms and pan ic disorder was observed in the multiplex families, using a variety of simu lations for dominant and recessive models of inheritance. However, LOD scor es of similar to 1.1 and 1.05 were observed for the DAT and DRD4 exon 1 loc i, respectively, The results reported here provide little support for the r ole of these polymorphisms in panic disorder, Am, J, Med. Genet. (Neuropsyc hiatr. Genet.) 96:324-330, 2000. (C) 2000 Wiley-Liss, Inc.