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

Brasil

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

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
Ethnicity			0.422^b
White	69.9%	64.8%
Not White	30.1%	35.2%
Body mass index (kg/m²)	28.8	28.9	0.874^a
Age of menopause	48.8	46.6	0.07^a
Hormonal therapy	10.7%	18.1%	0.09^b
Smoking	13.1%	20.1%	0.15^b
Arterial hypertension	57.8%	49.4%	0.186^b
Diabetes mellitus	24.5%	23.7%	0.888^b
Dyslipidemia	25.4%	24.7%	0.889^b
Chronic cough	1.8%	6.8%	0.08^b
Intestinal constipation	14.3%	10.4%	0.35^b
Pregnancy	4 (1–24)	3 (0–16)	< 0.0001^a
Parity	4 (1–16)	3 (0–15)	< 0.0001^a
Vaginal delivery	3 (0–16)	2 (0–15)	< 0.0001^a
Cesarean section	0 (0–1)	0 (0–3)	0.377^a
Heaviest birthweight (g)	3,516	3,059	0.147^a
Episiotomy	8.3%	9.2%	> 0.999^b
Labor analgesia	3.7%	4.8%	0.768^b
Home birth	25.9%	3.05%	< 0.0001^b
Hysterectomy	15.2%	15.6%	> 0.999^b
Exaggerated physical exercise	22.5%	14.1%	0.077^b
MMP9 genotypes			0.2749^c
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
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
TT + CT	6 (18.2%)	23 (21.90%)	0.807^a

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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[TFN1] Abbreviations: GG, wild homozygous; MMP9, matrix metalloproteinase-9; TG, heterozygous; TT, polymorphic homozygous.

[TFN2] Unpaired t-test.

[TFN3] Fisher exact test.

[TFN4] Chi-squared test.