Investigation of transcription factor AP-2beta genotype in women with premenstrual dysphoric disorder

Abstract

It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2β in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2β in regulatory regions, suggesting an involvement of AP-2β in these systems. The gene encoding AP-2β is located on chromosome 6p12–p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2β genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2β correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2β genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2β genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2β genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2β genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.