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Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse.

Publication ,  Journal Article
Wu, JM; Visco, AG; Grass, EA; Craig, DM; Fulton, RG; Haynes, C; Weidner, AC; Shah, SH
Published in: Obstet Gynecol
September 2012

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.

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Published In

Obstet Gynecol

DOI

EISSN

1873-233X

Publication Date

September 2012

Volume

120

Issue

3

Start / End Page

587 / 593

Location

United States

Related Subject Headings

  • White People
  • Severity of Illness Index
  • Risk
  • Polymorphism, Single Nucleotide
  • Pelvic Organ Prolapse
  • Obstetrics & Reproductive Medicine
  • Multivariate Analysis
  • Middle Aged
  • Matrix Metalloproteinase 9
  • Logistic Models
 

Citation

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Wu, J. M., Visco, A. G., Grass, E. A., Craig, D. M., Fulton, R. G., Haynes, C., … Shah, S. H. (2012). Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse. Obstet Gynecol, 120(3), 587–593. https://doi.org/10.1097/AOG.0b013e318262234b
Wu, Jennifer M., Anthony G. Visco, Elizabeth A. Grass, Damian M. Craig, Rebekah G. Fulton, Carol Haynes, Alison C. Weidner, and Svati H. Shah. “Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse.Obstet Gynecol 120, no. 3 (September 2012): 587–93. https://doi.org/10.1097/AOG.0b013e318262234b.
Wu JM, Visco AG, Grass EA, Craig DM, Fulton RG, Haynes C, et al. Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse. Obstet Gynecol. 2012 Sep;120(3):587–93.
Wu, Jennifer M., et al. “Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse.Obstet Gynecol, vol. 120, no. 3, Sept. 2012, pp. 587–93. Pubmed, doi:10.1097/AOG.0b013e318262234b.
Wu JM, Visco AG, Grass EA, Craig DM, Fulton RG, Haynes C, Weidner AC, Shah SH. Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse. Obstet Gynecol. 2012 Sep;120(3):587–593.

Published In

Obstet Gynecol

DOI

EISSN

1873-233X

Publication Date

September 2012

Volume

120

Issue

3

Start / End Page

587 / 593

Location

United States

Related Subject Headings

  • White People
  • Severity of Illness Index
  • Risk
  • Polymorphism, Single Nucleotide
  • Pelvic Organ Prolapse
  • Obstetrics & Reproductive Medicine
  • Multivariate Analysis
  • Middle Aged
  • Matrix Metalloproteinase 9
  • Logistic Models