Skip to main content
Erschienen in: International Urogynecology Journal 7/2010

01.07.2010 | Original Article

Suppression of lysyl oxidase gene expression by methylation in pelvic organ prolapse

verfasst von: John Klutke, Frank Z. Stanczyk, Qing Ji, Joseph David Campeau, Carl Georg Klutke

Erschienen in: International Urogynecology Journal | Ausgabe 7/2010

Einloggen, um Zugang zu erhalten

Abstract

Introduction and hypothesis

We measured promoter methylation in the LOX gene in women with pelvic organ prolapse and in women without prolapse.

Methods

Genomic DNA was isolated from the uterosacral ligaments of eight women with prolapse and eight women without prolapse as controls. Genomic DNA was digested with BamHI and underwent sodium bisulfite modification. The LOX gene promoter region of −246 to +74 was then amplified by PCR, cloned into PCR2.1-TOPO and transformed into an Escherichia coli DH5α strain. Amplified plasmid DNA samples containing the LOX gene promoter region from each woman were sequenced and methylated CpG islands were identified by sequence comparison.

Results

A total of 66 methylated CpG sites were found in the group of patients with prolapse, while only one methylated CpG site was found in the non-prolapse control group.

Conclusions

Methylation in the promoter region may suppress LOX gene expression in women with pelvic organ prolapse.
Literatur
1.
Zurück zum Zitat DeLancey JO (2005) The hidden epidemic of pelvic floor dysfunction: achievable goals for improved prevention and treatment. Am J Obstet Gynecol 192:1488–1495CrossRefPubMed DeLancey JO (2005) The hidden epidemic of pelvic floor dysfunction: achievable goals for improved prevention and treatment. Am J Obstet Gynecol 192:1488–1495CrossRefPubMed
2.
Zurück zum Zitat Petros P, Ulmsten U (1993) An integral theory and its method for the diagnosis and management of female urinary incontinence. Scan J Urol Nephrol 153:1–93 Petros P, Ulmsten U (1993) An integral theory and its method for the diagnosis and management of female urinary incontinence. Scan J Urol Nephrol 153:1–93
3.
Zurück zum Zitat Ulmsten U, Ekman G, Giertz G, Malmstrom A (1987) Different biomechanical composition of connective tissue in continent and stress incontinent women. Acta Obstet Gynecol Scand 66:455–457CrossRefPubMed Ulmsten U, Ekman G, Giertz G, Malmstrom A (1987) Different biomechanical composition of connective tissue in continent and stress incontinent women. Acta Obstet Gynecol Scand 66:455–457CrossRefPubMed
4.
Zurück zum Zitat Ulmsten U, Henriksson L, Johnson P, Varhos G (1996) An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J 7:81–86CrossRef Ulmsten U, Henriksson L, Johnson P, Varhos G (1996) An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J 7:81–86CrossRef
5.
Zurück zum Zitat Falconer C, Ekman-Ordeberg G, Ulmsten U, Westergren-Thorsson G, Barchan K, Malmstrom A (1996) Changes in paraurethral connective tissue at menopause are counteracted by oestrogen. Maturitas 24:197–204PubMed Falconer C, Ekman-Ordeberg G, Ulmsten U, Westergren-Thorsson G, Barchan K, Malmstrom A (1996) Changes in paraurethral connective tissue at menopause are counteracted by oestrogen. Maturitas 24:197–204PubMed
6.
Zurück zum Zitat Falconer C, Blomgren B, Johansson O, Ulmsten U, Malmstrom A, Westergren-Thorsson G et al (1998) Different organization of collagen fibrils in stress incontinent women of fertile age. Acta Obstet Gynecol Scand 77:87–97CrossRefPubMed Falconer C, Blomgren B, Johansson O, Ulmsten U, Malmstrom A, Westergren-Thorsson G et al (1998) Different organization of collagen fibrils in stress incontinent women of fertile age. Acta Obstet Gynecol Scand 77:87–97CrossRefPubMed
7.
Zurück zum Zitat Falconer C, Eckman-Ordeberg G, Blomgren B, Johansson O, Ulmsten U, Westergren-Thorsson G et al (1998) Paraurethral connective tissue in stress incontinent women after menopause. Acta Obstet Gynecol Scand 77:95–100CrossRefPubMed Falconer C, Eckman-Ordeberg G, Blomgren B, Johansson O, Ulmsten U, Westergren-Thorsson G et al (1998) Paraurethral connective tissue in stress incontinent women after menopause. Acta Obstet Gynecol Scand 77:95–100CrossRefPubMed
8.
Zurück zum Zitat Bergman A, Elia G, Chung D, Perelman N, Nimni ME (1994) Biochemical composition of collagen in continent and stress urinary incontinent women. Gynecol Obstet Invest 37:48–51CrossRefPubMed Bergman A, Elia G, Chung D, Perelman N, Nimni ME (1994) Biochemical composition of collagen in continent and stress urinary incontinent women. Gynecol Obstet Invest 37:48–51CrossRefPubMed
9.
Zurück zum Zitat Söderberg MW, Falconer C, Byström B, Malmström A, Ekman G (2004) Young women with genital prolapse have a low collagen concentration. Acta Obstet Gynecol Scand 83:1193–1198PubMed Söderberg MW, Falconer C, Byström B, Malmström A, Ekman G (2004) Young women with genital prolapse have a low collagen concentration. Acta Obstet Gynecol Scand 83:1193–1198PubMed
10.
Zurück zum Zitat Goepel C, Hefler L, Methfessel H, Koelbl H (2003) Periurethral connective tissue status of postmenopausal women with genital prolapse with and without stress incontinence. Acta Obstet Gynecol Scand 82:659–664PubMed Goepel C, Hefler L, Methfessel H, Koelbl H (2003) Periurethral connective tissue status of postmenopausal women with genital prolapse with and without stress incontinence. Acta Obstet Gynecol Scand 82:659–664PubMed
11.
Zurück zum Zitat Kobak W, Lu J, Hardart A, Zhang C, Stanczyk F, Felix J (2005) Expression of lysyl oxidase and transforming growth factor beta 2 in women with severe pelvic organ prolapse. J Reprod Med 50:827–831PubMed Kobak W, Lu J, Hardart A, Zhang C, Stanczyk F, Felix J (2005) Expression of lysyl oxidase and transforming growth factor beta 2 in women with severe pelvic organ prolapse. J Reprod Med 50:827–831PubMed
12.
Zurück zum Zitat Liu X, Zhao Y, Gao J, Pawlyk B, Starcher B, Spencer JA et al (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nature Genetics 36:178–182CrossRefPubMed Liu X, Zhao Y, Gao J, Pawlyk B, Starcher B, Spencer JA et al (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nature Genetics 36:178–182CrossRefPubMed
13.
Zurück zum Zitat Kaneda A, Wakazono K, Tsukamoto T, Watanabe N, Tatematsu YM (2004) Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. Cancer Research 64:6410–6415CrossRefPubMed Kaneda A, Wakazono K, Tsukamoto T, Watanabe N, Tatematsu YM (2004) Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. Cancer Research 64:6410–6415CrossRefPubMed
15.
Zurück zum Zitat Nichols DH, Randall CL (1989) Vaginal surgery, 3rd edn. Williams and Wilkins, Baltimore, pp 65–68 Nichols DH, Randall CL (1989) Vaginal surgery, 3rd edn. Williams and Wilkins, Baltimore, pp 65–68
16.
Zurück zum Zitat Klutke J, Ji Q, Campeau J, Starcher B, Felix JC, Stanczyk FZ, Klutke C (2008) Decreased endopelvic fascia elastin content in pelvic organ prolapse. Acta Obstet Gynecol Scand 87:111–115CrossRefPubMed Klutke J, Ji Q, Campeau J, Starcher B, Felix JC, Stanczyk FZ, Klutke C (2008) Decreased endopelvic fascia elastin content in pelvic organ prolapse. Acta Obstet Gynecol Scand 87:111–115CrossRefPubMed
17.
18.
Zurück zum Zitat Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMed Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMed
19.
Zurück zum Zitat Csiszar K (2001) Lysyl oxidases: a novel multifunctional amine oxidase family. Prog Nucleic Acid Res Mol Biol 70:1–32CrossRefPubMed Csiszar K (2001) Lysyl oxidases: a novel multifunctional amine oxidase family. Prog Nucleic Acid Res Mol Biol 70:1–32CrossRefPubMed
20.
Zurück zum Zitat Nikolava G, Lee H, Berkovitz S, Nelson S, Sinsheimer J, Vilain E, Rodriguez LV (2007) Sequence variant in the laminin gamma1 (LAMC1) gene associated with familial pelvic organ prolapse. Hum Genet 120:847–856CrossRef Nikolava G, Lee H, Berkovitz S, Nelson S, Sinsheimer J, Vilain E, Rodriguez LV (2007) Sequence variant in the laminin gamma1 (LAMC1) gene associated with familial pelvic organ prolapse. Hum Genet 120:847–856CrossRef
21.
Zurück zum Zitat Skorupski P, Miotla P, Jankiewicz K, Rechberger T (2007) Polymorphism of the gene encoding alpha-1 chain of collagen type I and a risk of pelvic organ prolapse—a preliminary study. Ginekol Pol 78:852–855PubMed Skorupski P, Miotla P, Jankiewicz K, Rechberger T (2007) Polymorphism of the gene encoding alpha-1 chain of collagen type I and a risk of pelvic organ prolapse—a preliminary study. Ginekol Pol 78:852–855PubMed
22.
Zurück zum Zitat Kim J, Kim JY, Song KS, Lee YH, Seo JS, Jelinek J, Glodshmidt-Clermont PJ, Issa JP (2006) Epigenetic changes in estrogen receptor ß gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochem Biophys Acta 1772:72–80PubMed Kim J, Kim JY, Song KS, Lee YH, Seo JS, Jelinek J, Glodshmidt-Clermont PJ, Issa JP (2006) Epigenetic changes in estrogen receptor ß gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochem Biophys Acta 1772:72–80PubMed
Metadaten
Titel
Suppression of lysyl oxidase gene expression by methylation in pelvic organ prolapse
verfasst von
John Klutke
Frank Z. Stanczyk
Qing Ji
Joseph David Campeau
Carl Georg Klutke
Publikationsdatum
01.07.2010
Verlag
Springer-Verlag
Erschienen in
International Urogynecology Journal / Ausgabe 7/2010
Print ISSN: 0937-3462
Elektronische ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-010-1108-2

Weitere Artikel der Ausgabe 7/2010

International Urogynecology Journal 7/2010 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.