Mutations in Four Genes More Prevalent in Women with Endometriosis, Study Suggests

Mutations in Four Genes More Prevalent in Women with Endometriosis, Study Suggests

Women with endometriosis have an increased burden of mutations in four genes, called ZNF586, LUZP4, POP4 and UNC5CL, new data from Predictive Laboratories show.

This is the first time these four genes have been implicated in endometriosis. The data will help understand the genetic basis of endometriosis and may also identify new mechanisms of disease, as well as aid in new diagnostic tools and the development of new therapeutic approaches.

Moreover, this genetic analysis may help identify risk factors for endometriosis-associated conditions, such as infertility. This is the goal of a collaboration established between Thermo Fisher Scientific and Predictive Laboratories.

Kenneth Ward, MD, shared the results in a presentation, “Excess germline mutations in four genes in unrelated women with surgical endometriosis,” at the 2019 European Society of Human Reproduction and Embryology (ESHRE), in Vienna, Austria.

Endometriosis is caused by complex interplay among the immune system and hormones, the environment and genetic factors.

Identifying whether genetic mutations underlie the risk for developing endometriosis is key to improving diagnosis and in the search for more effective therapies.

While some mutations have been found in cases of familial endometriosis, up to now no highly mutated genes have been identified as risk factors for non-familial endometriosis.

The goal of Predictive Laboratories, a subsidiary of Predictive Technology Group, is to determine the genetic basis of endometriosis using whole exome sequencing.

Genes, which are composed of DNA sequences, are transcribed into molecules called RNA. In turn, RNA molecules are used as templates to make proteins, which carry out various functions in a cell. Whole exome sequencing involves determining the sequence of the gene regions with instructions for making proteins, called protein-coding regions, or exons, in our DNA.

In this study, researchers performed whole exome sequencing in DNA samples extracted from either the blood or saliva of 2,596 unrelated women with surgically confirmed endometriosis. The aim was to identify genes carrying a higher burden of mutations in women with endometriosis compared to the general population.

They identified four genes — ZNF586, LUZP4, POP4, and UNC5CL — with a significantly higher mutation rate in endometriosis. While mutated in 8% of the general population, the genes were mutated in 25% of women with the disease.

Moreover, this is the first time these genes and, subsequently, their coded proteins are being identified as potential risk factors for endometriosis.

“Predictive Laboratories is committed to comprehensive disease management and advancing research into the genetic cause of endometriosis to improve the diagnosis and management of patients suffering from the disease,” Bradley Robinson, CEO of Predictive Technology Group, said in a press release. “Our investment in technology has led to the identification of additional germline DNA changes associated with endometriosis.”

Women with endometriosis are also at higher risk of infertility. A report of the American College of Obstetrics and Gynecology (ACOG) says that infertility is seen in at least 40% of women with endometriosis. Despite this high prevalence, whether infertility has a genetic basis is poorly known.

Thermo Fisher Scientific is collaborating with Predictive Laboratories to better understand the genetics of infertility, and to more accurately identify women who are at risk of infertility.

“We look forward to this exciting and important work with Predictive Laboratories to better understand infertility in women,” Yan Zhang, general manager, reproductive health for Thermo Fisher, said in another press release. “With the combination of our partner’s expertise and our advanced solutions for genetic analysis, we are committed to reducing the future financial and emotional burden couples face while undergoing fertility treatment.”

“Our research may lead to a better understanding of the [development] of endometriosis,” said Ward, the laboratory director of Predictive Laboratories. “Given the pace of innovation for targeted therapy, we are thrilled to present clinically relevant insights that may result in improved treatment of infertility as a result of endometriosis.”