Natural Gene Variants May Protect Against Endometriosis

Natural Gene Variants May Protect Against Endometriosis

In a new study entitled “Evaluation of Tumor Necrosis Factor Alpha Polymorphism Frequencies in Endometriosis,” researchers investigated how natural variants (polymorphisms) within the promoter region of the tumor necrosis factor-alpha (TNF-α) gene associate with endometriosis. The study was published in the International Journal of Fertility & Sterility.

TNF-α is a potent immunomodulator and proinflammatory cytokine regulating immune system responses. Its role has been implicated in the pathogenesis of autoimmune and infectious diseases. TNF-α was detected in peritoneal fluid (a liquid that lubricates the surface of the tissue that lines the abdominal wall and pelvic cavity) of women with endometriosis. These results suggest a link between endometriosis and the immune system, and in fact anti-TNF therapy is currently included in endometriosis treatment.

From a genetic point of view, studies have suggested that TNF-α gene polymorphisms (natural variations in a gene carrying no adverse effects) associate with endometriosis in several ethnic populations; however, the results were frequently incompatible between studies.

Researchers investigated the association between the -1031 T/C, -238 G/A and -308 G/A polymorphisms on a specific region of the TNF-α gene (called promoter) and endometriosis, enrolling 65 endometriosis patients (with stages II, III, or IV endometriosis as confirmed by laparoscopy) and 65 matched healthy controls at the Beheshti Hospital. Patients’ peripheral blood was collected from all participants, along with clinical data and personal and family histories. After blood collection, patients’ DNA was isolated from white blood cells and TNF-α gene polymorphisms analyzed by polymerase chain reaction (PCR).

The PCR analysis revealed a strong association between -1031 T/C polymorphism in the promoter region of the TNF-α gene with endometriosis in this Iranian population. Specifically, the researchers observed a decrease in the -1031 T/C polymorphism in the most severe cases of endometriosis. On the contrary, no association was observed with the other two TNF-α polymorphisms, -238 G/A and -308 G/A, and endometriosis.

Findings from the study suggest that the -1031T polymorphism may carry a protective role in endometriosis progression. However, additional studies are required to further confirm these results in a larger cohort of endometriosis patients. If confirmed, however, the -1031 T/C polymorphism may be used as a biomarker to identify women at risk of developing endometriosis.