Supervisors: prof Helle Karro (TÜ naistekliinik), prof Raivo Uibo (TÜ bio- ja siirdemeditsiini instituut) ja prof Andres Salumets
(TÜ bio- ja siirdemeditsiini instituut, TÜ naistekliinik).
Opponent: professor Krina Tynke Zondervan, MSc, DPhil. (Oxfordi Ülikool, Ühendkuningriik)
Endometriosis is a common chronic gynaecological disease defined by the presence of endometrial-like tissue outside the uterus, mainly on the ovaries and peritoneal wall, but sometimes also in the urinary tract, bowel wall, etc. Monthly bleeding from these lesions causes local inflammatory reaction and the formation of adhesions. In some cases the disease may remain asymptomatic, but often it is associated with severe pelvic pain and infertility, thus having a major impact both on women suffering from it as well as on their families. Since the 'gold standard' for the diagnosis of endometriosis is laparoscopic visualization of lesions, the right diagnosis is often delayed for years. Endometriosis is a complex disease and its exact aetiology is not clear yet. It is likely that different factors like genetic predisposition, impaired immune function and environmental factors are involved in disease development. Identifying the genes that influence susceptibility to endometriosis could help us understand better various disease mechanisms and thus would aid in the development of more effective diagnostic and therapeutic methods. The aim of the present study was to analyse associations between endometriosis and different candidate genes. Thus, DNA samples from 199 healthy women and 150 endometriosis patients were collected and the frequencies of different genetic variants were compared between the two groups. In addition, to verify whether autoantibodies against survivin, a protein expressed in endometriotic lesions, could be used as a biomarker of endometriosis, their level was measured in the sera of 98 patients and 47 women with similar complaints but without the disease. Out of ten genes that were analysed, five showed an association with endometriosis. These genes encode for proteins involved in oestrogen biosynthesis (17β-hydroxysteroid dehydrogenase type 1) and function (oestrogen receptor β), tissue remodelling (matrix metalloproteinases 2 and 9) and angiogenesis (vascular endothelial growth factor). Instead, the gene encoding for oestrogen receptor α seemed to be more associated with female infertility. It was also found that anti-survivin antibodies cannot be used as a diagnostic marker, since their level is similar in women with and without endometriosis. In conclusion, this study gave new knowledge about the genetics of endometriosis, but further research is needed to clear the exact function of these genetic variants.