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

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This case–control study found the COX-2 ancestral allele −765G associated with endometriosis risk and increased COX-2 gene expression in women with endometriosis.

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This case–control study evaluated the frequency of the COX-2 promoter G-765C (rs20417) polymorphism and its relationship to COX-2 (PTGS2) expression in eutopic endometrium in 365 Brazilian women with laparoscopically and histologically confirmed endometriosis (251 infertile, 114 fertile) versus 522 fertile controls without endometriosis, with endometrial biopsies performed in subsets for qRT-PCR analysis. Genotypes were determined by high-resolution melt, and COX-2 mRNA expression was quantified by TaqMan qRT-PCR normalized to GAPDH; among women with fertile moderate/severe endometriosis, the ancestral −765G allele distribution differed significantly from controls and was associated with increased endometriosis risk (p = 0.028; OR 0.53; CI 0.32–0.90). The mean COX-2 mRNA expression in the endometrium of women with endometriosis was higher than in controls (3.85 vs 2.84, p = 0.028). The paper’s limitation is that only 37 endometriosis cases and 47 controls underwent endometrial biopsy for expression analysis, limiting power for expression comparisons. This paper is centrally about endometriosis — it links the COX-2 promoter G-765C polymorphism with COX-2 expression in eutopic endometrium and risk of moderate/severe endometriosis associated with fertility.

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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. Similar content being viewed by others

References

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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. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare there are no conflicts of interest. Rights and permissions About this article Cite this article 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 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-015-3808-9

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endometriosis

MeSH descriptors

Cyclooxygenase 2 Endometriosis Endometrium Gene Expression Polymorphism, Genetic Promoter Regions, Genetic Adult Alleles Biopsy Brazil Brazil Case-Control Studies Cyclooxygenase 2 Cyclooxygenase 2 Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female

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