New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study

OBJECTIVE: Endometriosis is a common gynaecological disease, associated with severe pelvic pain and reduced fertility; however, molecular mechanisms remain largely unknown. Genome-wide association studies (GWAS) are able to identify genetic loci, which can play significant role during endometriosis development. AIM: The study aimed at localisation of new genes and chromosomal loci, the nucleotide variants of which determine the level of susceptibility to endometriosis. STUDY DESIGN: Blood samples from 171 patients with endometriosis were used as material for studies. The patients were recruited to the study at the Department of Operative Gynaecology of the Institute of the Polish Mother's Memorial Hospital in Lodz. A control group (n=2934) came from the POPULOUS collection registered at Biobank Lab, Department of Molecular Biophysics, University of Lodz. DNA of the patients with endometriosis was compared with DNA of women free from that disease, the comparison being supported by GWAS. RESULTS: Genome-wide significant correlation was identified between one new, not previously described, single nucleotide polymorphism (SNP), rs10129516, localised on chromosome 14 in intergenic region between PARP1P2 and RHOJ genes (p=1.44×10-10, OR=3.104, 95% CI=2.329-4.136) and endometriosis. We have also identified significant association with endometriosis of 18 SNPs localised on chromosome 6 in position range 31883957 - 32681631 (C2 and HLA-DRA genes region) with the lowest observed p value for rs644045 in C2 gene (p=2.04×10-8, OR=1.955, 95% CI=1.541-2.480). CONCLUSION: Reported GWAS identified the novel loci associated with endometriosis in Polish women, not previously reported. The most interesting observation shown in our study are regions associated with susceptibility to endometriosis of loci located near C2, HLA-DRA and RHOJ genes. RESULTS: of that study did not correspond to previously published data about polymorphism in that regions and further evaluations are necessary in groups with higher numbers of patients to explain whether the above-mentioned genetic variant may be the risk factor for pathogenesis of endometriosis.