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العنوان
GENETIICS OF PREMENSTRUAL
DYSPHORIIC DIISorder /
المؤلف
Elshourbagy,Maged Mahmoud Ali Ahmed.
هيئة الاعداد
باحث / Maged Mahmoud Ali Ahmed Elshourbagy
مشرف / Mohamed Nabegh Elmahallawy
مشرف / Waleed Hitlar Tantawy
مشرف / Shaughn O’Brien
تاريخ النشر
2014
عدد الصفحات
222p.;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
أمراض النساء والتوليد
تاريخ الإجازة
1/1/2014
مكان الإجازة
جامعة عين شمس - كلية الطب - أمراض النساء والتوليد
الفهرس
Only 14 pages are availabe for public view

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Abstract

Premenstrual 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.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.Materials and Methods:
The study included 53 women with clinically diagnosed
premenstrual dysphoric disorder and 52 healthy control subjects.
The 5-HTTLPR promoter polymorphism was genotyped in both
groups by PCR and gel electrophoreses. The rs25531 single
nucleotide polymorphism was also genotyped in both groups by
doing PCR and digestion with the restriction enzyme MspI
which recognizes and cut the G variant only. Genotyping was
done by two independent researchers that were unaware of the
clinical group status. Genotype and allele frequencies for the
composite 5-HTTLPR/rs25531 marker were analyzed by Chisquare
test.
Statistical analysis
Genotype distribution was tested regarding conformity to
Hardy-Weinberg equilibrium. Fisher exact probability tests were
used to test any specific genotype distribution between the
PMDD and control group with the use of StatXact version 4.0.1
(Cytel Corp, Cambridge, MA). The test is considered
statistically significant if the exact p value is less than 0.05.
Results:
Genotype distribution has shown conformity to Hardy-
Weinberg equilibrium. There was no significant association between any of rs25531 SNP or the 5-HTTLPR/rs25531
composite marker and either the premenstrual dysphoric
disorder or the control groups. Neither the triallelic classification
nor the functional classification of the genotypes proved any
association with any of the two groups of the study.