CYP2C19 polymorphism increases the risk of endometriosis
Estrogen metabolizing gene mutations can be associated with defective hormonal signaling leading to disease processes. Endometriosis is an estrogen dependent that can be influenced by defective signaling in the estrogen pathway.
To evaluate the association of A/G 85952 CYP2C19 and A/G 937 HSD17B1 gene polymorphisms with endometriosis through the investigation of a large Brazilian sample of women with endometriosis and a fertile control group.
Five hundred women with endometriosis and 500 women without endometriosis were tested for CYP2C19 and HSD17B1 polymorphisms, by TaqMan Real Time PCR. The results were statistically analyzed by chi-square, logistic regression and tested for Hardy-Weinberg equilibrium.
The comparison of genotype and allelic frequency of CYP2C19 polymorphism (rs11592737) in patients with endometriosis and control group showed a statistically significant difference (p = 0.0203) and for the HSD17B1 polymorphism (rs605059) differences were not significant (p = 0.0687). Comparing the stages I/II and III/IV endometriosis with the control group for the CYP2C19 we observed p = 0.0133 and p = 0.0564, respectively, and for HSD17B1 the values for p = 0.4319 and p = 0.0667.
We observed that CYP2C19 polymorphism is associated with endometrisis in Brazilian women and can be considered a potential biomarker of the disease.
KeywordsEndometriosis CYP2C19 HSD17B1 Infertility Molecular biomarsker
The authors thank the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scientific initiation scholarship granted by the graduate student Amanda Sonnewend and scientific grant #470333/2013-8.
- 4.Painter JN, Nyholt DR, Morris A, Zhao ZZ, Henders AK, Lambert A, et al. High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19. Fertil Steril. 2011;95(7):2236–40.Google Scholar
- 11.Mannermaa A, Peltoketo H, Winqvist R, Ponder B, Kiviniemi H, Easton D, et al. Human familial and sporadic breast cancer: analysis of the coding regions of the 17β-hydroxysteroid dehydrogenase 2 gene (EDH17B2) using a single-strand conformation polymorphism assay. Hum Genet. 1994;93:319–24.PubMedCrossRefGoogle Scholar
- 12.Revised American Society for Reproductive Medicine classification of endometriosis; 1996, Fertil Steril. 1997; 67(5):817–821.Google Scholar
- 17.Dunning AM, Dowsett M, Healey CS, Tee L, Luben RN, Folkerd E, et al. Polymorphisms Associated With Circulating Sex Hormone Levels in Postmenopausal Women. Journal of the National Cancer Institute 2004; 96 (12).Google Scholar
- 24.Bukulmez O, Hardy DB, Carr BR, Auchus RJ, Toloubeydokhti T, Word RA, et al. Androstenedione up-regulation of endometrial aromatase expression via local conversion to estrogen: potential relevance to the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2008;93(9):3471–7.PubMedCentralPubMedCrossRefGoogle Scholar
- 25.Santos RP, Encinas F, Lasmar RB, Granjeiro JM, Penna IA. Polimorfismos nos genes MMP2, MMP13, CYP1A1, GSTM1 e EMX2 e endometriose. Femina. 2011;39(6):316.Google Scholar