Assessment of Metalloproteinase Matrix 9 (MMP9) Gene Polymorphisms Risk Factors for Pelvic Organ Prolapse in the Brazilian Population

Ghersel, Frederico Rezende; Souto, Ricardo Peres; Gonzales, Ester Wilma Pacheco; Paulo, Denise Souza; Fernandes, César Eduardo; Oliveira, Emerson

doi:10.1055/s-0039-1681112

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev. Bras. Ginecol. Obstet. 41 (3) • Mar 2019 • https://doi.org/10.1055/s-0039-1681112 copy

Assessment of Metalloproteinase Matrix 9 (MMP9) Gene Polymorphisms Risk Factors for Pelvic Organ Prolapse in the Brazilian Population

Avaliação de polimorfismos de genes de matriz de metaloproteinase 9 (MMP9) como fatores de risco para o prolapso de órgãos pélvicos na população brasileira

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To evaluate the C-1562T matrix metalloproteinase 9 (MMP9) gene polymorphisms as risk factors related to the occurrence of pelvic organ prolapse (POP) and to identifytheclinicalvariablesassociatedwith theoccurrenceof thedisease.Epidemiological studies of risk factors for POP do not explain why nulliparous women with no known risk factors also develop POP. Therefore, genetic factors may be involved.

Methods

Cohort study with 86 women with symptomatic POP (cases), and 158 women withoutapriororcurrentdiagnosisof thisdisorder(controls).Thegroupswereanalyzedfor the presence of MMP9 gene polymorphisms. Genotyping was performed using polymerase chainreaction(PCR)with DNA obtained froma peripheral venouspuncture ofboth groups.

Results

There were no differences between the cases and controls even when we grouped the mutant homozygous and heterozygous genotypes. The analysis of patients with a complete absence of POP versus patients with total POP also showed no statistically significant differences. Ageand home birth were found to be independent risk factors for POP.

Conclusions

There were no statistically significant differences in the C-1562T MMP9 polymorphisms between the cases and controls in Brazilian women.

Keywords:
polymorphism; matrix metalloproteinase; pelvic organ prolapse

Variables	Cases(Mean, median, or %)	Controls(Mean, median, or %)	p-value
Age (years)	68.4	57.8	< 0.0001^a Unpaired t-test.
Ethnicity			0.422^b Fisher exact test.
White	69.9%	64.8%
Not White	30.1%	35.2%
Body mass index (kg/m²)	28.8	28.9	0.874^a Unpaired t-test.
Age of menopause	48.8	46.6	0.07^a Unpaired t-test.
Hormonal therapy	10.7%	18.1%	0.09^b Fisher exact test.
Smoking	13.1%	20.1%	0.15^b Fisher exact test.
Arterial hypertension	57.8%	49.4%	0.186^b Fisher exact test.
Diabetes mellitus	24.5%	23.7%	0.888^b Fisher exact test.
Dyslipidemia	25.4%	24.7%	0.889^b Fisher exact test.
Chronic cough	1.8%	6.8%	0.08^b Fisher exact test.
Intestinal constipation	14.3%	10.4%	0.35^b Fisher exact test.
Pregnancy	4 (1–24)	3 (0–16)	< 0.0001^a Unpaired t-test.
Parity	4 (1–16)	3 (0–15)	< 0.0001^a Unpaired t-test.
Vaginal delivery	3 (0–16)	2 (0–15)	< 0.0001^a Unpaired t-test.
Cesarean section	0 (0–1)	0 (0–3)	0.377^a Unpaired t-test.
Heaviest birthweight (g)	3,516	3,059	0.147^a Unpaired t-test.
Episiotomy	8.3%	9.2%	> 0.999^b Fisher exact test.
Labor analgesia	3.7%	4.8%	0.768^b Fisher exact test.
Home birth	25.9%	3.05%	< 0.0001^b Fisher exact test.
Hysterectomy	15.2%	15.6%	> 0.999^b Fisher exact test.
Exaggerated physical exercise	22.5%	14.1%	0.077^b Fisher exact test.
MMP9 genotypes			0.2749^c Chi-squared test.
GG	73 (84.8%)	126 (79.7%)
TG	13 (15.2%)	28 (17.7%)
TT	0%	4 (2.6%)
Grouped MMP9 genotypes			0.3890^b Fisher exact test.
GG	73 (84.8%)	126 (79.7%)
TG + TT	13 (15.2%)	32 (20.3%)

Genotypes	POP stage IV (n= 33)	POP stage 0 (n= 105)	p-value
GG	27 (81.8%)	82 (78.10%)	0.807^a Fisher exact test.
TT + CT	6 (18.2%)	23 (21.90%)	0.807^a Fisher exact test.

Covariate	Crude OR(CI)	p-value	Adjusted OR(CI)	p-value
Age ≥ 51	15.57 (4.73–51.2)	< 0.0001	11.89 (3.53–40)	< 0.0001
Pregnancy ≥ 3	2.02 (1.24–3.28)	0.004	0.656 (0.283–1.51)	0.325
Vaginal delivery ≥ 3	3.12 (1.86–5.23)	< 0.0001	1.91 (0.7–5.22)	0.202
Parity ≥ 3	2.64 (1.62–4.31)	< 0.0001	2.01 (0.665–6.1)	0.216
Home birth	11.1 (4.14–29.7)	< 0.0001	9.645 (3.35–27.7)	< 0.0001

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[1] Address for correspondence
Frederico Rezende Ghersel, PhD, Departamento de Uroginecologia e Cirurgia Vaginal, Disciplina de Ginecologia, Faculdade de Medicina do ABC, Av. Lauro Gomes, 2000, Santo André, SP, 09060-870, Brazil (e-mail: frederico@osite.com.br).