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Published on: September 13, 2022
Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse
Jennifer M Wu1, Anthony G Visco, Elizabeth A Grass
1Department of Obstetrics and Gynecology, Division of Urogynecology, Center for Human Genetics, Duke University, Durham, North Carolina 27707, USA. jennifer.wu@duke.edu
Objective:
Matrix metalloproteinase-9 (MMP9) is a protease associated with degradation of collagen and elastin. Because increased MMP9 activity in vaginal tissue has been associated with pelvic organ prolapse (POP), we sought to comprehensively estimate MMP9 genetic variants and the risk for advanced prolapse.
Methods:
This is a candidate gene association study of women with stage III-IV prolapse (case group, n=239) and women with stage 0-1 prolapse (control group, n=197). We attempted to oversample "extreme" phenotypes, including younger women with severe prolapse and older women without prolapse, in an attempt to concentrate the genetic effect. We used a linkage disequilibrium tagged approach to identify single nucleotide polymorphisms in MMP9 to evaluate in our study. To minimize potential confounding by race, our analysis focused on non-Hispanic white women. We performed multivariable logistic regression to estimate the association between MMP9 single nucleotide polymorphisms and case-control status, adjusting for age and vaginal parity.
Results:
Women with advanced prolapse were slightly younger (64.8 ± 10.3 compared with 69.0 ± 10.2 years, P<.001) and more likely to have had one or more vaginal deliveries (96.6% compared with 82.2%, P<.001) when compared with control participants. Eight single nucleotide polymorphisms were assessed, which represented 93% coverage of the MMP9 gene. Of these, two were associated with advanced prolapse: 1) rs3918253 (adjusted odds ratio [OR] 0.64, 95% confidence interval [CI] 0.41-1.0, P=.05); and 2) rs3918256 (adjusted OR 0.64, 95% CI 0.41-1.01, P=.05).
Conclusion:
MMP9 is a biologically plausible candidate gene for POP given our results.
Insights
Genetic variants in matrix metalloproteinase-9 (MMP9) were associated with advanced pelvic organ prolapse (POP) risk in non-Hispanic white women. This suggests MMP9 is a potential genetic factor in POP development.
Area of Science:
- Genetics
- Biochemistry
- Gynecology
Background:
- Matrix metalloproteinase-9 (MMP9) is an enzyme involved in tissue degradation.
- Elevated MMP9 activity in vaginal tissue is linked to pelvic organ prolapse (POP).
Purpose of the Study:
- To investigate the association between genetic variants of MMP9 and the risk of advanced POP.
- To identify specific MMP9 single nucleotide polymorphisms (SNPs) related to POP.
- To analyze genetic factors contributing to POP in a targeted population.
Main Methods:
- A candidate gene association study comparing women with advanced POP (stage III-IV) and controls (stage 0-I).
- Focused on non-Hispanic white women to minimize racial confounding.
- Utilized a linkage disequilibrium-tagged approach to select SNPs in the MMP9 gene.
- Employed multivariable logistic regression, adjusting for age and parity.
Main Results:
- Two MMP9 SNPs, rs3918253 and rs3918256, showed a statistically significant association with advanced POP.
- Women with advanced POP were younger and more likely to have had vaginal deliveries.
- The identified SNPs were associated with a reduced odds of advanced prolapse (OR=0.64 for both).
Conclusions:
- MMP9 represents a biologically plausible candidate gene for POP.
- Specific genetic variants in MMP9 may influence the risk of developing advanced pelvic organ prolapse.
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