Abstract
Objective
To evaluate the frequency of polymorphism G-765C (rs20417) of the COX-2 gene and the expression of this gene in the endometrium of women with endometriosis.
Study design
This is a case–control study of 365 women with endometriosis (251 infertile and 114 fertile) submitted to laparoscopy/laparotomy with histological confirmation of endometriosis. The control group was composed of 522 fertile women without endometriosis. Of these, 37 patients from the endometriosis group and 47 from the control group were submitted to biopsy of the endometrium for analysis of the expression of the COX-2 gene. The genotypes were determined using analysis by High-Resolution Melt. Gene expression was measured by qRT-PCR with TaqMan methodology using the GAPDH gene as normalizer of the reactions.
Results
The distribution of the genotypes and alleles in the group of fertile women with moderate/severe endometriosis showed a statistically significant difference, demonstrating association of the ancestral allele, −765G, with increased risk of endometriosis (p = 0.028; OR 0.53; CI 0.32–0.90). The mean expression of the COX-2 gene (mRNA PTGS2) in the group of women with endometriosis was statistically higher compared to the control group (3.85 versus 2.84, p = 0.028).
Conclusion
The present study identified that in Brazilian women the presence of the ancestral allele, −765G, of the COX-2 gene is associated with an increased risk for development of moderate/severe endometriosis associated with fertility, and that the eutopic endometrium of women with endometriosis showed increased expression of COX-2 when compared to the control group.
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References
Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:342–345
Barbosa CP, Souza AM, Bianco B, Christofolini D, Mafra FA, Lima GR (2009) Frequency of endometriotic lesions in peritoneum samples from asymptomatic fertile women and correlation with CA125 values. São Paulo Med J 127:342–345
Barbosa CP, Souza AM, Bianco B, Crhistofolini D, Mafra FA, Lima GR (2010) OC-125 immunostaining in endometriotic lesion samples. Arch Gynecol Obstret 281:43–47
Bianco B, Lerner TG, Trevisan CM, Cavalcanti V, Christofolini D, Barbosa CP (2012) The nuclear fator-kB functional promoter polymorphism is associated with endometriosis and infertility. Hum Immunol 73:1190–1193
Abrao MS, Muzii L, Marana R (2013) Anatomical causes off female infertility and their management. J Gynaecol Obstret 123(Supl 2):S18–S24
Peluso C, Christofolini DM, Goldman CS, Mafra FA, Cavalcanti V, Barbosa CP, Bianco B (2013) TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility. Hum Immunol 74:93–97
Hla T, Nielson K (1992) Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci 89:7384–7388
Kosaka T, Miyata A, Ihara H, Sugimoto T, Takeda O, Takahashi E, Tanabe T (1994) Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxidase synthase2. Eur J Biochem 221:889–897
Carvalho WA, Carvalho RDS, Rios-Santos F (2004) Analgésicos inibidores específicos da ciclooxigenase-2: avanços terapêuticos. Rev Bras Anest 54:448–456
Sales KJ, Jabbour HN (2003) Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium. Reproduction 126:559–567
Morita I (2002) Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat 68–69:165–175
Milne AS, Jabbour HN (2003) Prostaglandin (PG) F (2alpha) receptor expression. And signaling in human endometrium: role of PGF (2alpha) in epithelial cell proliferation. J Clin Endocrinol Metab 88:1825–1832
Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, Laurent GJ (2002) Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 22:1631–1636
The American Fertility Society (1997) The American Fertility Society: revised American Society for Reproductive Medicine Classification of Endometriosis 1996. Fertil Steril 67:817–821
Lahiri DK, Nurnberger JLJR (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19(19):5444
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression. Data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408
Bottini N, Bottini E, Gloria-Bottini F, Mustelin T (2002) Low-molecular-weight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms. Arch Immunol Ther Exp (Warsz) 50(2):95–104
Lattrich C, Häring J, Schüler S, Skryzpczak M, Ortmann O, Treeck O (2014) Polymorphisms in the promoter region of estrogen receptor β gene in endometrial cancer. Arch Gynecol Obstet 289:631–635
Wang X, Huang M, Zhang X, Hua R, Guo W (2013) COX-2-765G > C polymorphism increases the risk of cancer: a meta-analysis. PLoS One 8:1–9
Salazar LA, Inostroza M, Jara C, Veja F, Garcia R, Ciuffardi I, Gusman N (2010) Association of −765G > C polymorphism of the COX-2 gene with recurrent embryo implantation failure in Southern Chilean women. Clin Chim Acta 411:1822–1824
Kim HY, Cho S, Choi YS, Yang HI, Lee KE, Seo SK, Lee BS (2012) Cyclooxygenase-2 (COX2) gene -765G/C polymorphism and advanced-stage endometriosis in Korean women. Am J Reprod Immunol 68:238–243
Piranda DN, Festa-Vasconcellos J, Amaral LM, Bergmann A, Vianna-Jorge R (2010) Polymorphisms in regulatory regions of cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study. Biomed Central 10:1–9
Alves-Silva J, Santos MS, Guimarães PE, Ferreira AC, Bandelt HJ, Pena SD et al (2000) The ancestry of Brazilian mtDNA lineages. Am J Hum Gent 67:444–461
Cho NH, Park YK, Kin YTK, Yang H, Kim S (2004) Lifetime expression of stem cell markers in the uterine endometrium. Fertil Steril 81:403–407
Lessey BA, Lebovic DI, Taylor RN (2013) Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects. Semin Reprod Med 2:109–124
Harada T, Kaponis A, Iwabe T, Taniguchi F, Makrydimas G, Sofikitis N et al (2004) Apoptosis in human endometrium and endometriosis. Hum Reprod Update 1:29–38
Wang D, Chen Q, Zhang C, Ren F, Li T (2012) DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis. Eur J Med Res 17:1–6
Cho S, Park SH, Choi YS, Seo SK, Kim HY, Park KH et al (2010) Expression of cyclooxygenase-2 in eutopic endometrium and ovarian endometriotic tissue in women with severe endometriosis. Gynecol Obstet Invest 69:93–100
Chen Q, Zhang C, Chen Y, Lou J, Wang D (2012) Identification of endometriosis-related genes by representational difference analysis of cDNA. Aust N Z J Obstet Gynaecol 52:140–145
Ota H, Igarashi S, Sasaki M, Tanaka T (2001) Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Human Reprod 16:561–566
Acknowledgments
The authors wish to thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) for the financial aid of the project (2012/03564-0) and the scholarship to the student Tatiana Guida Ponce (2013/07978-6), and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the scholarship to the student Viviane Maria Bezerra Cavalcanti Lins.
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Cavalcanti, V., Ponce, T.G., Mafra, F.A. et al. Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women with endometriosis. Arch Gynecol Obstet 293, 109–115 (2016). https://doi.org/10.1007/s00404-015-3808-9
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DOI: https://doi.org/10.1007/s00404-015-3808-9