Association of Multiple DRD2 Polymorphisms with Anorexia Nervosa

Abstract

To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The À141 C/À insertion/deletion (À141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the À141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of 450 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…Complimenting these functional magnetic resonance imaging (fMRI) studies is a report of higher 11  C-raclopride binding potential in the ventral striatum in women who were recovered from AN, suggesting that DA activity is enhanced in this population [343], and significant relations between multiple DRD 2 polymorphisms and AN [344]. …”

Neurobiology of anorexia and bulimia nervosa

“…Reduced CSF DA metabolites occur in malnourished individuals with AN (60) and persist after recovery (92). Individuals with AN have altered frequency of functional polymorphisms of DA D2 receptor genes that might affect receptor transcription and translation efficiency (93). The anteroventral striatum (AVS) and dorsal caudate are components of limbic and executive-associative pathways (94)(95)(96).…”

Anorexia nervosa: Towards an integrative neuroscience model

“…Molecular genetics has demonstrated abnormalities of monoamine related genes in AN including polymorphism of serotonin (5 HT) and dopamine (DA) receptor genes, 5HT2a (Kaye, Bailer et al, 2005;Kaye, Frank et al, 2005) and D2 (Bergen et al, 2005). In particular these alterations in 5HT and DA receptor density have been shown to be concentrated in limbic system in AN (Kaye, 2008), a part of the brain integral to the regulation of emotion.…”