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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald


CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

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1877-8879
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Volume 18, Issue 1

Issues

The MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain-intensity in pregnant women

Aqsa Khalid Mahmood / Aurora Moen / Signe Nilssen Stafne
  • Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
  • Clinical Service, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hilde Stendal Robinson
  • Department of Health Science, Institute of Health and Society, University of Oslo, Oslo, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nina Køpke Vøllestad
  • Department of Health Science, Institute of Health and Society, University of Oslo, Oslo, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kjell Åsmund Salvesen
  • Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
  • Clinical Service, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Siv Mørkved
  • Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
  • Clinical Service, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Johannes Gjerstad
Published Online: 2018-02-14 | DOI: https://doi.org/10.1515/sjpain-2017-0168

Abstract

Background and aims:

Matrix metalloproteinase 9 (MMP9) is an enzyme that may affect degradation of several extracellular matrix (ECM) components in the pelvic ligaments during pregnancy. Previous studies indicate that genetic variations in the gene encoding MMP9 may affect the enzymatic activity. One such genetic variant is a single nucleotide polymorphism (SNP), rs17576 A>G. In this study we investigated whether the MMP9 SNP rs17576 A>G may be associated with increased lumbopelvic pain in 838 pregnant woman. The study was registered with ClinicalTrials.gov (NCT 00476567) on May 21, 2007.

Methods:

Lumbopelvic pain-intensity was measured by visual analog scale (VAS) at two time points during pregnancy, T1 (18–22 weeks), T2 (32–36 weeks) and 3 months after delivery. Blood samples were collected at each point and SNP genotyping was carried out using predesigned TaqMan SNP genotyping assays.

Results:

The results showed a significant association between the number of G alleles and pain-intensity in the evening at T2. The pain among G/G carriers was higher than among A/G carriers, which in turn was higher than among the A/A carriers. The most pronounced association between the G allele and pain-intensity was observed in primiparae.

Conclusions:

We conclude that the MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain-intensity during pregnancy. The present data support the hypothesis that lumbopelvic pain during pregnancy may be related to a relaxin – MMP9 – tissue remodeling mechanism.

Implications:

The present findings may be important for future mechanistic studies on how MMP9 rs17576 A>G may affect changes in the ECM components in pelvic ligaments and lumbopelvic pain-intensity during pregnancy.

Keywords: MMP9; relaxin; lumbopelvic pain; pelvic girdle pain; polymorphism

References

  • [1]

    Gutke A, Ostgaard HC, Oberg B. Pelvic girdle pain and lumbar pain in pregnancy: a cohort study of the consequences in terms of health and functioning. Spine (Phila Pa 1976) 2006;31:E149–55.CrossrefPubMedGoogle Scholar

  • [2]

    Robinson HS, Mengshoel AM, Bjelland EK, Vollestad NK. Pelvic girdle pain, clinical tests and disability in late pregnancy. Man Ther 2010;15:280–5.Web of SciencePubMedCrossrefGoogle Scholar

  • [3]

    Sydsjo G, Sydsjo A. Newly delivered women’s evaluation of personal health status and attitudes towards sickness absence and social benefits. Acta Obstet Gynecol Scand 2002;81:104–11.PubMedCrossrefGoogle Scholar

  • [4]

    Wu WH, Meijer OG, Uegaki K, Mens JM, van Dieen JH, Wuisman PI, Ostgaard HC. Pregnancy-related pelvic girdle pain (PPP), I: terminology, clinical presentation, and prevalence. Eur Spine J 2004;13:575–89.CrossrefPubMedGoogle Scholar

  • [5]

    Albert H, Godskesen M, Westergaard J. Prognosis in four syndromes of pregnancy-related pelvic pain. Acta Obstet Gynecol Scand 2001;80:505–10.PubMedCrossrefGoogle Scholar

  • [6]

    Calguneri M, Bird HA, Wright V. Changes in joint laxity occurring during pregnancy. Ann Rheum Dis 1982;41:126–8.PubMedCrossrefGoogle Scholar

  • [7]

    Bani D. Relaxin: a pleiotropic hormone. Gen Pharmacol 1997;28:13–22.CrossrefPubMedGoogle Scholar

  • [8]

    Vollestad NK, Torjesen PA, Robinson HS. Association between the serum levels of relaxin and responses to the active straight leg raise test in pregnancy. Man Ther 2012;17:225–30.Web of SciencePubMedCrossrefGoogle Scholar

  • [9]

    Unemori EN, Amento EP. Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts. J Biol Chem 1990;265:10681–5.PubMedGoogle Scholar

  • [10]

    Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, Yamashita K, Hayakawa T. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem 1992;267:21712–9.PubMedGoogle Scholar

  • [11]

    Katsuda S, Okada Y, Okada Y, Imai K, Nakanishi I. Matrix metalloproteinase-9 (92-kd gelatinase/type IV collagenase equals gelatinase B) can degrade arterial elastin. Am J Pathol 1994;145:1208–18.PubMedGoogle Scholar

  • [12]

    Reponen P, Sahlberg C, Munaut C, Thesleff I, Tryggvason K. High expression of 92-kDa type IV collagenase (gelatinase) in the osteoclast lineage during mouse development. Ann N Y Acad Sci 1994;732:472–5.PubMedCrossrefGoogle Scholar

  • [13]

    Alexander CM, Hansell EJ, Behrendtsen O, Flannery ML, Kishnani NS, Hawkes SP, Werb Z. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development 1996;122:1723–36.PubMedGoogle Scholar

  • [14]

    Lenhart JA, Ryan PL, Ohleth KM, Palmer SS, Bagnell CA. Relaxin increases secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 during uterine and cervical growth and remodeling in the pig. Endocrinology 2001;142:3941–9.PubMedCrossrefGoogle Scholar

  • [15]

    Cao WH, Liu HM, Liu X, Li JG, Liang J, Liu M, Niu ZH. Relaxin enhances in-vitro invasiveness of breast cancer cell lines by upregulation of S100A4/MMPs signaling. Eur Rev Med Pharmacol Sci 2013;17:609–17.PubMedGoogle Scholar

  • [16]

    Chen HY, Lin WY, Chen YH, Chen WC, Tsai FJ, Tsai CH. Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in Taiwanese women. Eur J Obstet Gynecol Reprod Biol 2010;149:222–4.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [17]

    Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet 2008;82:1122–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • [18]

    Han YJ, Kim HN, Yoon JK, Yi SY, Moon HS, Ahn JJ, Kim HL, Chung HW. Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis. Fertil Steril 2009;91:2324–30.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [19]

    Brooks R, Kizer N, Nguyen L, Jaishuen A, Wanat K, Nugent E, Grigsby P, Allsworth JE, Rader JS. Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer. Gynecol Oncol 2010;116:539–43.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [20]

    Stafne SN, Salvesen KA, Romundstad PR, Stuge B, Morkved S. Does regular exercise during pregnancy influence lumbopelvic pain? A randomized controlled trial. Acta Obstet Gynecol Scand 2012;91:552–9.CrossrefWeb of ScienceGoogle Scholar

  • [21]

    Shipley JM, Doyle GA, Fliszar CJ, Ye QZ, Johnson LL, Shapiro SD, Welgus HG, Senior RM. The structural basis for the elastolytic activity of the 92-kDa and 72-kDa gelatinases. Role of the fibronectin type II-like repeats. J Biol Chem 1996;271: 4335–41.CrossrefPubMedGoogle Scholar

  • [22]

    Zhang B, Henney A, Eriksson P, Hamsten A, Watkins H, Ye S. Genetic variation at the matrix metalloproteinase-9 locus on chromosome 20q12.2-13.1. Hum Genet 1999;105:418–23.PubMedCrossrefGoogle Scholar

  • [23]

    Hu Z, Huo X, Lu D, Qian J, Zhou J, Chen Y, Xu L, Ma H, Zhu J, Wei Q, Shen H. Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer. Clin Cancer Res 2005;11:5433–9.CrossrefPubMedGoogle Scholar

  • [24]

    Naqvi T, Duong TT, Hashem G, Shiga M, Zhang Q, Kapila S. Relaxin’s induction of metalloproteinases is associated with the loss of collagen and glycosaminoglycans in synovial joint fibrocartilaginous explants. Arthritis Res Ther 2005;7: R1–11.PubMedCrossrefGoogle Scholar

  • [25]

    Samuel CS, Coghlan JP, Bateman JF. Effects of relaxin, pregnancy and parturition on collagen metabolism in the rat pubic symphysis. J Endocrinol 1998;159:117–25.PubMedCrossrefGoogle Scholar

  • [26]

    Ahmad N, Wang W, Nair R, Kapila S. Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-zeta pathways. Mol Cell Endocrinol 2012;363:46–61.CrossrefWeb of SciencePubMedGoogle Scholar

About the article

Corresponding author: Johannes Gjerstad, Prof., National Institute of Occupational Health, PB 8149 Dep., 0033 Oslo, Norway, Tel.: +47 23 19 52 54, Fax: +47 23 19 52 00


Received: 2017-11-22

Revised: 2017-12-19

Accepted: 2017-12-25

Published Online: 2018-02-14

Published in Print: 2018-01-26


Authors’ statements

Research funding: The study was supported by a grant from the Central Norway Regional Health Authority.

Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could lead to potential conflicts of interest.

Informed consent: The participants received written information and signed informed consent forms.

Ethical approval: The study was performed in accordance with the Helsinki Declaration and approved by the Regional Committee for Medical and Health Research Ethics (REK 4.2007.81).

Authors’ contributions

AKM, AM, SNS, SM and JG performed the research. AKM, AM, SNS, SM and JG analyzed the data. AKM, AM, SNS, SM, HSR, NKV, KS and JG drafted the manuscripts. AKM and JG wrote the paper. HSR, NKV, SM and JG designed the study. All authors read and approved the final manuscript.

Availability of data and materials

All data underlying the findings may be available upon request. Requests for the data should be addressed to Director General Pål Molander or Director of Communication Sture Bye at National Institute of Occupational Health (NIOH), Norway: postmottak@stami.no.


Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 1, Pages 93–98, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2017-0168.

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