Molecular Pathogenesis of Endometriosis; Toll-Like Receptor-4 A896G (D299G) Polymorphism: A Novel Explanation

Madhavi Latha, Sirisha Vaidya, Sireesha Movva, Srinivas Chava, Sujatha Govindan, Suresh Govatati, Manjula Banoori, Qurratulain Hasan, Vijay Lakshmi Kodati
Genetic testing and molecular biomarkers · 2011 · vol. 15(3) , pp. 181–184 · doi:10.1089/gtmb.2010.0178 · PMID:21214494 · W2028650750
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This study found that the TLR4 A896G polymorphism's G allele and GG genotype were associated with an increased risk of endometriosis, potentially promoting peritoneal inflammation and endometrial cell adhesion.

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Abstract

BACKGROUND: Endometriosis is a distressing gynecological disorder. Toll-like receptor 4 (TLR4) is specific for recognition of the molecular pattern of gram-negative bacteria. TLR4 is present on the surface of endometrial cells. Their role in the molecular pathogenesis of endometriosis is postulated through a novel explanation. OBJECTIVE: To study the TLR4 A896G polymorphism in cases of endometriosis and age- and sex-matched healthy controls and evaluate its role in the molecular pathogenesis of endometriosis. DESIGN: Case-control study, involving patients from four gynecological centers from Hyderabad Samples: The study was carried out on 400 women who include 200 surgically confirmed cases of endometriosis and 200 healthy women volunteers in whom endometriosis was excluded by the standard diagnostic criteria. RESULTS: An association of G allele, GG, and AG genotype of TLR4 A896G polymorphism was seen in cases of endometriosis. "G" allele was found to be significantly associated with endometriosis (odds ratio=4.4827; 95% confidence interval: 2.2829-8.8021; χ(2) p<0.0001). An eightfold increase of endometriosis risk was seen in women who carry GG genotype, whereas AA genotype can be considered as protective in our population. CONCLUSION: TLR4 A896G polymorphism (rs4986790) is a functional polymorphism resulting in hypo-responsiveness of the receptor, thus resulting in peritoneal inflammation. The molecular microenvironment becomes favorable for the endometrial cells to adhere to the peritonium, thereby resulting in the initiation of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Disease Susceptibility Endometriosis Polymorphism, Genetic Toll-Like Receptor 4 White People Alleles Case-Control Studies Endometriosis Endometriosis Female Gene Frequency Genotype Humans India Odds Ratio Toll-Like Receptor 4 White People

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