Low-penetrance genes are associated with increased susceptibility to endometriosis

Objective: To investigate whether genetic polymorphisms of CYP1A1, GSTM1, a nd GSTT1 are associated with endometriosis. Design: Genetic polymorphism analysis. Setting: University department. Patient(s): A family with four women in two generations who had endometrios is and one member with suspected endometriosis in the third generation were compared with a group of fertile women. Intervention(s): Laparoscopic examination. Main Outcome Measure(s): Blood specimens were obtained from fertile females and available affected female family members. Multiplex polymerase chain r eaction (PCR) and restriction fragment length polymorphism PCR was done to determine each participant's genotype. Result(s): All affected family members had genotype CYP1A1 wt/ml and GSTM1 null deletion. The frequency of this genotype in 54 fertile women was 13%. A 17-year-old family member with suspected endometriosis bad the same genot ype. One affected member was also a carrier of a GSTT1 null deletion. This combination was not found in any of the fertile participants. The most freq uent genotypes in the sample were CYP1A1 wt/wt, with GSTM1 null deletion an d at least one functional allele of GSTT1, and CYP1A1 wt/wt, with at least one functional allele of GSTM1 and GSTT1 (33% and 31%, respectively). Conclusion(s): The combination of CYP1A1 ml polymorphism and GSTM1 null del etion is closely associated with penetration of the endometriosis phenotype , whereas GSTT1 null deletion may add to the penetration of this trait.