In a new study entitled “Functional evaluation of genetic variants associated with endometriosis near GREB1,” a team of researchers performed a genetic analysis of endometrium samples from women affected by endometriosis and identified a potential new single nucleotide polymorphisms (SNPs) that may play a role in the risk to develop endometriosis. The study was published in the journal Human Reproduction.

Endometriosis is one of the most frequent genealogical disorders affecting women in reproductive ages and is characterized by growth of endometrial tissue outside the uterine cavity. Symptoms include dysmenorrhea, dyspareunia, irregular uterine bleeding and
 reduced fertility. The variety of symptoms often results in significant delays in diagnosis and since no current cure is known, the need for a better understanding of disease pathogenesis is urgent. Several reports have suggested that endometriosis may have a genetic basis. In fact, genome-wide association studies (GWAS) identified 10 genomic regions for endometriosis. Specific genes from these genes need to be identified to characterize how they may associate with endometriosis pathophysiology.

Recently, a research team evaluated whether a variation in the DNA sequence of a particular gene, the growth regulation by estrogen in breast cancer 1 (GREB1) gene, is associated with endometriosis. Since GREB1 is an estrogen-regulated gene identified in breast cancer cell lines and tumors, it is possible that GREB1 plays a role in an estrogen-dependent disease like endometriosis.

The team analyzed blood and/or endometrial tissue samples provided by females and performed a comprehensive genomic analysis for single nucleotide polymorphisms (SNPs) within the GREB1 genomic region (SNPs are single base-pair differences in the DNA sequence of an individual). They identified a new SNP that exhibited a high association with endometriosis risk. Notably, the new SNP association was found even stronger then a different GREB1 SNP, reported in a previous study.

Further studies were performed to validate their findings and analyzed the protein expression for GREB1 in samples of endometrium from women positive and negative for endometriosis, as well as the effects of SNP variation on expression of GREB1. However, they found no significant differences in the expression levels between the two groups. The authors also found that the identified SNPs did not alter GREB1 expression, either at the gene and protein level. However, the authors found that GREB1 expression was modulated in a cell and hormone-specific manner in endometrium.

The authors hypothesize that using whole endometrium tissue may dilute the effect of the SNPs and this may be the reason why they see no phenotype. As such, they suggest that follow-up studies with a larger sample size are required to assess the role for GREB1 SNPS in increasing the risk of developing endometriosis.