Gene Variation Identified in Endometriosis, Opening New Doors for Treatment

2021-08-26

A group of scientists from the Nuffield Department of Women's & Reproductive Health at Oxford University may have found a potential key to finally treating endometriosis, a disease that affects around 176 million women worldwide. In the study, Nuffield head and reproductive and genomic epidemiology professor Krina Zondervan and team conducted a genetic analysis of 32 families where at least three women had been diagnosed with endometriosis. They collected and sequenced DNA samples to study genetic linkage signals on chromosome 7p13-15 and found a significant overrepresentation of low-frequency coding variants in NPSR1. They also found the same receptor in their study of non-human primates (rhesus macaques, mouse models) with endometriosis. Although the authors said that further study is required to make conclusions, the findings give hope for a possible non-hormonal treatment approach for endometriosis. In an interview, Zondervan and co-author Dr. Thomas Tapmeier said that the decision to explore both human and non-human primate gene models is mainly because rhesus macaques menstruate the same way as women and can show similar endometriosis symptoms, like period pain and infertility. Endometriosis is a chronic inflammatory condition that causes pelvic pain and infertility in women, with limited treatment options and 50 percent heritability. At present, its treatment modalities are either surgical or hormonal. Typically, it takes eight years before women are diagnosed with the disease and, by this time, the symptoms are already apparent. NPSR1, the main point of the research, is responsible for encoding the protein Neuropeptide S receptor 1. Variations of this gene have previously been linked to other inflammatory diseases like inflammatory bowel disease and asthma and psychological problems like sleep disorders, panic attacks, and anxiety. In the latest study, the researchers found that the NPSR1 inhibitor SHA 68R blocked the NPSR1-mediated signaling, proinflammatory TNF-α release, and monocyte chemotaxis in vitro — all leading to a notable reduction of inflammatory cell infiltrate and abdominal pain in mouse models. Zondervan, Tapmeier, and their team said that further study is needed to understand the link between genetic variations in NPSR1 and tissue-specific functions of the receptor and the proteins where it binds.

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