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Endometriosis is a chronic, painful disease that affects the female genital tract with unknown definite etiology, though there are multiple theories that try to explain its etiology. Genetic causes are suggested in the most widely accepted theories, and this study examined the association between the HSD17B1 gene polymorphism and endometriosis and its severity.Twenty-five patients with clinical suspicion of endometriosis confirmed by laparoscopic examination were admitted to the Gynecology and Obstetrics Department in the Minia University Hospital, and 25 women were enrolled as controls. All subjects underwent genetic analysis for the HSD17B1 gene polymorphism.There were significant associations between genotyping analysis of the cases and controls: G/G, A/G and A/A distributions among the cases were 8%, 60% and 32%, respectively, while in controls, they were 60%, 32% and 8%, respectively (p = 0.002, p = 0.05 and p = 0.03, respectively). There were no associations between the HSD17B1 gene polymorphism and severity of endometriosis.Genetic analysis of the HSD17B1 gene polymorphism showed it to have an important role in the etiology of endometriosis. Extensive further studies are recommended for further genes that may be associated with endometriosis.