GENETICS OF PREMENSTRUAL DYSPHORIC DISORDER

Abstract

Introduction remenstrual syndrome (PMS) is characterized by recurrent psychologic, somatic and/or behavioral symptoms that occur specifically during the luteal phase of the menstrual cycle, and resolve by menstruation. The symptoms are severe enough to affect the quality of life. At the end of the PMS spectrum comes the Premenstrual dysphoric disorder (PMDD) with predominant psychologic symptoms. PMDD is estimated to occur in 3% to 8% of women with PMS.1 Although the exact cause of PMDD is unknown, however, there is evidence implicate an underlying dysregulation of serotonergic pathway. Evidence from epidemiologic studies suggests genetic factor contribution to PMDD.9-Most investigations have focused on the serotonin transporter gene (SLC6A4), which encodes a membrane-bound serotonin transporter responsible for active reuptake of serotonin from the synaptic cleft. It is also the site of action of selective serotonin reuptake inhibitors (SSRIs) which proved to be effective in the treatment of up to 70% of women suffering from PM DD. P Summary and Conclusion 137 The most frequently studied polymorphism of SLC6A4 is the serotonin transporter long promoter region which comprises a complex of 20 to 23 base-pair (bp) repeat elements. A 43 bp insertion/deletion that produces a long (L) or a short (S) allele. The S variant has been associated with lower transcriptional activity of SLC6A4 and has a been linked to major depressive disorders and SSRI response in Caucasian subjects. A functional A/G single nucleotide polymorphism (SNP rs25531) that is located immediately upstream of the 43 bp insertion/deletion site further classify the L allele to La and Lg .23-24 The later has been shown to lower 5-HTT expression in vitro. Because the SNP is very rare to be found in the S alleles. Many studies currently consider 5-HTTLPR as a triallelic marker: LA, LG and S(A or G). Functionally, both alleles LG and S(A or G) are associated with low expression of the transporter protein. Objective: To investigate whether the function serotonin transporter long promoter region (5-HTTLPR) / rs25531 promoter polymorphism in the serotonin transporter gene is associated with premenstrual dysphoric disorder.