1. International Neurourology Journal 2015;19:164-170
Is There a Relationship Between Pelvic Organ Prolapse and Tissue Fibrillin-1 Levels?
Ayla Eser1, Eylem Unlubilgin2, Fatih Hizli3, Muradiye Acar4, Zeynep Kamalak5, Aydin Kosus1, Nermin Kosus1, Deniz Hizli1, Esra Gunduz4
1Department of Obstetrics and Gynecology, Turgut Ozal University Medical School, Ankara, Turkey
2Department of Obstetrics and Gynecology, Etlik Zubeyde Hanim Training and Research Hospital, Ankara, Turkey
3Department of Urology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey
4Department of Medical Genetics, Turgut Ozal University Medical School, Ankara, Turkey
5Department of Obstetrics and Gynecology, Nenehatun Maternity Hospital, Erzurum, Turkey
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (
org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2. International Neurourology Journal 2015;19:164-170
INTRODUCTION
Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated.
Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed.
We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse.

3. International Neurourology Journal 2015;19:164-170
MATERIALS AND METHODS
Thirty women undergoing colporrhaphy or hysterectomy because of cystocele, rectocele, cystorectocele, or uterine prolapse were assigned to a pelvic prolapse study group, and thirty women undergone hysterectomy for nonpelvic prolapse conditions were assigned to a control group.
Real-time polymerase chain reaction was conducted on vaginal tissue samples to measure the expression of Fibrillin- 1. Expression levels were compared between study and control groups by Mann-Whitney U test with Bonferroni revision.

4. International Neurourology Journal 2015;19:164-170
RESULTS
Fibrillin-1 gene expression was not significantly lower in the study group than in the control group.
Similarly, no significant correlation between Fibrillin-1 levels and grade of pelvic prolapse was found.
Age over 40 years (P=0.018) and menopause (P=0.027) were both associated with reduced Fibrillin-1 levels in the pelvic prolapse group, whereas the delivery of babies weighing over 3,500 g at birth was associated with increased Fibrillin-1 expression (P=0.006).

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CONCLUSIONS
The results did not indicate a significant reduction in Fibrillin-1 gene expression in pelvic prolapse disorders; however, reduced Fibrillin-1 may contribute to increased pelvic organ prolapse risk with age and menopause.
Increased Fibrillin-1 gene expression may be a compensatory mechanism in cases of delivery of babies with high birth weight. Further studies are needed for a better understanding of these observations.

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Table. 1. Demographic characteristics of women in study and control groups
Characteristic
Study group (n = 30)
Control group (n = 30)
P-value
Age (yr)
45.5 (27–71)
47 (26–53)
0.899
Parity (n)
3 (1–5)
2 (1–5)
0.324
Body mass index (kg/m2)
28.5 (23–39)
29.3 (23–45)
0.221
Vaginal deliveries (n)
1 (1–3)
0.352
Delivery weight (g)
3,525 (3,200–3,800)
3,400 (2,700–4,750)
0.339
Menopause, n (%)
0.008*
 Yes
18 (60)
27 (90)
 No
12 (40)
3 (10)
Postmenopausal period (yr)
0 (0–26)
0 (0–6)
0.009*
Fibrillin-1 level
0.066 (0.005–0.429)
0.085 (0.010–0.439)
0.114
Values are presented as median (range) unless otherwise indicated.
*P<0.05 was considered statistically significant.

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Table. 2. Surgery indications
Group
No. (%)
Study (n = 30)
 Uterine prolapse
6 (20.0)
 Rectocele
3 (10.0)
 Cystorectocele
18 (60.0)
 Cystocele
Control (n=30)
 DUB
10 (33.3)
 Endometrial hyperplasia
1 (3.3)
 Myoma uteri
19 (63.3)
DUB, dysfunctional uterine bleeding.

8. Table. 3. Surgery indications
International Neurourology Journal 2015;19:
Table. 3. Surgery indications
Fibrillin-1
Postmenopausal period
Age
Body mass index
Gravidity
Parity
Vaginal delivery
Delivery weight
Cystocele stage
Rectocele stage
Cystorectocele stage
Case
 Rho
–0.420
–0.520a)
–0.140
–0.188
–0.332
0.243
0.413a)
–0.037
0.101
0.038
 P-value
0.032*
0.006*
0.496
0.358
0.097
0.232
0.036*
0.858
0.625
0.852
Control
0.051
0.015
0.023
–0.057
–0.009
–0.110
–0.241 -
0.794
0.939
0.905
0.770
0.965
0.569
0.207
*P<0.05 was considered statistically significant.
a)Rho was considered as significant correlation.

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Table. 4. Association between demographic characteristics and Fibrillin-1 ratio in the pelvic prolapse group
Demographic attribute
No.
Fibrillin-1
P-value
Age (yr)
0.018*
 < 40 15
0.075 (0.005–0.429)
 ≥ 40
0.035 (0.015–0.103)
Parity
0.083  2 12
0.081 (0.0345–0.429)  3 10
0.036 (0.021–0.092)
0.043*,a)  4 4
0.072 (0.064–0.075)
 ≥5
0.015 (0.005–0.056)
0.049*,b)
Vaginal deliveries
0.403  1 24
0.047 (0.005–0.429)
0.080 (0.067–0.084) 2
0.064 (0.049–0.079)
Body mass index (kg/m2)
0.782
 < 25 6
0.077 (0.021–0.103)
 25–30 14
0.058 (0.015–0.429)
 ≥ 30
0.056 (0.005–0.092)
Delivery weight (g)
0.006*
 < 3,500
0.029 (0.005–0.075)
 ≥ 3,500 20
0.078 (0.021–0.429)
Menopause (n)
0.027*
 Yes 18
0.032 (0.015–0.103)
 No
0.076 (0.005–0.429)
Postmenopausal period (yr)
0.889
 < 5
0.034 (0.021–0.047)
 ≥ 5
Values are presented as median (range).
*P<0.05 was considered statistically significant.
a)Comparing parity 2 and 3. b)Comparing parity 2 and 5.

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Table. 5. Distribution of Fibrillin-1 values according to pelvic prolapse type
POP surgery
No.
Fibrillin-1
P-value
Only cystocele 3
0.054 (0.021–0.080)
0.718
Only rectocele
0.077 (0.015–0.098)
Cystorectocele 18
0.049 (0.005–0.429)
Cystocele, POP-Q stage
0.294  1 1
0.005 (-)  2 8
0.049 (0.021–0.080)  3 10
0.064 (0.015–0.429)  4 5
0.041 (0.028–0.092)
Rectocele, POP-Q stage
0.304
0.049 (-) 19
0.041 (0.015–0.080)
0.072 (0.021–0.429)
Uterine prolapse
0.231
 Yes 6
0.047 (0.021–0.072)
 No 22
0.075 (0.005–0.429)
Values are presented as median (range).
POP, pelvic organ prolapse; POP-Q, POP quantification.

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Table. 6. Distribution of Fibrillin-1 values according to pelvic prolapse type
Demographic attribute
Study group
Control group
P-value
Age (yr)
 < 40
0.075 (0.005–0.429)
0.041 (-)
0.400
 ≥ 40
0.035 (0.015–0.103)
0.085 (0.010–0.439)
0.026*
 P-value
0.018*
0.552
Menopause (n)
 Yes
0.032 (0.015–0.103)
0.092 (0.021–0.383)
0.469
 No
0.076 (0.005–0.429)
0.080 (0.010–0.439)
0.501
0.027*
0.866
Values are presented as median (range).
POP, pelvic organ prolapse.
*P<0.05 was considered statistically significant.

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Fig. 1

13. International Neurourology Journal 2015;19:164-170
Fig. 1

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Fig. 1. Amplification plots of Fibrillin-1 mRNA (A) and housekeeping β-actin mRNA (B). Serial dilutions of Fibrillin-1 and β-actin cDNA plasmids were prepared and amplification was performed by quantitative real-time polymerase chain reaction. For each dilution, fluorescence is plotted against the cycle number. Log concentration and cycle numbers of each dilution are shown. Serial dilutions of Fibrillin-1 and β-actin cDNA plasmids were prepared and amplification was performed. Log concentrations of Fibrillin-1 mRNA (C) and β-actin mRNA (D) were plotted against the cycle number.