Role of L-Selectin Gene P213S Polymorphism and Macrophage Profiles (M1, M2) in Cases of Endometriosis

Henry Salim Siregar

Abstract


Objective: To determine the presence of an L-selectin gene P213S polymorphism in association with the pathogenesis of endometriosis.Design : Comparative analytical study using a 2 population case-control design.Setting : Department of Obstetrics and Gynaecology at Haji Adam Malik General Hospital, Dr. Pirngadi Medan Hospital, networking hospitals and private clinics throughout Medan from Januray 2013 - March 2014. Population: Reproductive aged women complaining menstrual pain, abdominal located bulging, and/or infertility. Through consecutive sampling, patients suspected with endometriosis and meeting the inclusion criteria were taken as samples. The case group comprised of women diagnosed with endometriosis whereas the control group consisted of non endometriosis women.Methods : Visiting gynecology outpatient clinic patients were taken a complete history, and underwent physical/gynecological, sonographic examinations to determine an indication to perform a laparoscopy/laparotomy and, if present, a laparoscopy was scheduled to take place during the proliferation phase. Presence of endometriosis was assessed during the procedure, and further confirmed by histopathologically reviewing peritoneal specimens. Patients diagnosed with endometriosis were categorized into the case group, after which severity degrees were determined based on the Revised Classification of the American Sociey for Reproductive Medicine 1997. Non endometriosis patients were categorized into the control group based on inclusion and exclusion criterias. Peritoneal tissues were sampled and 5 cc of blood taken. DNA isolation and genotyping was then performed, whereas peritoneal tissue samples were histopatahologically and immunohistochemically examined. Data were univariately and bivariately analyzed. Descriptive data was univariately analyzed.Main Outcome Measures           : CD68, CD 163, M1 and M2.Results            : S allele subjects had a 2,893 (95% CI; 1,135-7,373) higher risk of developing endometriosis than P allele subjects (p<0,05). PS and SS genotyped subjects had a 3,556 higher risk of devolping endometriosis than their PP genotyped counterparts (95% CI; 1,049-12,052, p-value 0,041). CD163 was more frequently expressed than CD68 in endometriosis lesions (60,870 ±28,939 vs 34,783 ±18,194, p-value 0,0001). Positive immunohistochemical scorings revealed CD68 macrophages were less frequently expressed (69,96%) than CD163 macrophages (100%) (p-value 0,0001).Conclusion          : L-selectin gene P213S polymorphism is associated with endometriosis. M2 Macrophage has a more significant role in developing endometriosis than M1 macrophage.


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