{"paper_id":"2c9be8bb-e8ea-4f55-95e4-e50bad08fdef","body_text":"Abstract\nPurpose\nTo investigate the role of genetic variations and expression alterations of BRCA1 and BRCA2 genes in the pathophysiology of endometriosis.\nMethods\nA genetic association study was conducted in 573 endometriosis cases and 490 controls of Indian origin. We genotyped 13 selected promoter SNPs of BRCA1 gene and 2 selected promoter SNPs of BRCA2 gene by PCR-sequencing analysis. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of BRCA1 & 2 was analyzed in the eutopic endometria of endometriosis cases and controls by western-blot and immunohistochemical analysis.\nResults\nOur results revealed significant association between BRCA1 rs71361504 (−/GTT) SNP and endometriosis risk in Indian women (P < 0.0001), while the remaining SNPs of both BRCA1 & 2 genes showed no difference between cases and controls. Western-blot and immunohistochemical analysis revealed significantly decreased BRCA1 expression levels in eutopic endometria of patients compared with controls (P < 0.05). Furthermore, nuclear BRCA1 was frequently lost compared with cytoplasmic BRCA1 in eutopic endometria of patients. Expression of BRCA2 did not differ between patients and controls.\nConclusions\nBRCA1 rs71361504 SNP may modify the endometriosis risk in Indian women. In addition, decreased expression of BRCA1 may play an important role in the pathophysiology of endometriosis. The analysis of BRCA1 genetic variants and/or expression might help to identify patients at high risk for disease outcome.\nSimilar content being viewed by others\nReferences\nGiudice LC, Kao LC. Endometriosis. Lancet. 2004;364:1789–99.\nSpuijbroek MD, Dunselman GA, Menheere PP, Evers JL. Early endometriosis invades the extracellular matrix. Fertil Steril. 1992;58:929–33.\nGovatati S, Kodati VL, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M. 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Dr. Suresh Govatati would like to thank Council of Scientific and Industrial Research (CSIR), India for JRF (NET) and SRF (NET).\nConflict of interest\nThe authors declare that they have no conflict of interest.\nFunding\nThis study was supported by grants from the Science & Engineering Research Board (SERB), India (Lr No: SR/FT/LS-188/2009) to M.B.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nAdditional information\nCapsule BRCA1 alterations may modify the endometriosis risk in Indian women. The analysis of BRCA1 genetic variants and/or expression might help to identify patients at high risk for disease outcome.\nElectronic supplementary material\nBelow is the link to the electronic supplementary material.\nSupplemental Table 1 (download DOC )\n(DOC 41 kb)\nSupplemental Table 2 (download DOC )\n(DOC 42 kb)\nRights and permissions\nAbout this article\nCite this article\nGovatati, S., Challa, K., Reddy, S.B. et al. BRCA1 alterations are associated with endometriosis, but BRCA2 alterations show no detectable endometriosis risk: a study in Indian population. J Assist Reprod Genet 32, 277–285 (2015). https://doi.org/10.1007/s10815-014-0379-9\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s10815-014-0379-9","source_license":"CC0","license_restricted":false}