Genetic association study of polymorphisms FOXP3 and FCRL3 in women with endometriosis.

Objective: To consider a possible cumulative effect of two genetic polymorphisms (FOXP3 C-2383T/rs3761549 and FCRL3 C-169T/rs7528684) that were previously shown to be associated with endometriosis.

Design: Genetic association study.

Setting: Human reproduction outpatient clinic of Faculdade de Medicina do ABC.

Patient(s): One hundred eighty-eight infertile women with endometriosis and 169 controls.

Intervention(s): Detection of polymorphisms FOXP3 (C-2383T/rs3761549) and FCRL3 (C-169T/rs7528684) by TaqMan real-time polymerase chain reaction. The results were analyzed statistically.

Main Outcome Measure(s): Genotype distribution, allele frequency, and combination analysis of the FOXP3 and FCRL3 polymorphisms.

Result(s): Single-marker analysis revealed a significant association of FOXP3 C-2383T and FCRL3 C-169T, independently, with endometriosis-related infertility, regardless of the stage of the disease. Considering the combined genotypes of FCRL3 and FOXP3 polymorphisms, a positive association was found between genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT and the risk of endometriosis development. Moreover, a progression of the disease risk was observed according to the presence of one or two copies of risk allele FCRL3 C and only one copy of risk allele FOXP3 T (odds ratio [OR] = 2.14, OR = 3.25, and OR = 6.0, respectively, for genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT).

Conclusion(s): Our findings support a possible gene-gene interaction leading to a cumulative effect on endometriosis development.