Estrogen receptor α dinucleotide repeat and cytochrorne P450c17α gene polymorphisms are associated with susceptibility to endometriosis

Objective: To investigate the association of endometriosis with estrogen receptor alpha (ER alpha) and cytochrome P450c17 alpha (CYP17) gene polymorphisms in light of the fact that estrogen plays a role in the pathogenesis of endometriosis and the CYP17 enzyme is involved with estrogen biosynthesis. Design: Prospective study. Setting: Genetics and gynecology units. Patient(s): All patients were divided into two groups: group 1, women with endometriosis (n = 119); group 2, normal controls (n = 108). Intervention(s): A dinucleotide (thymine-adenine [TA]) repeat polymorphism lying upstream of the ER alpha gene and A1/A2 polymorphism of the CYP17 gene were amplified by polymerase chain reaction, enzyme restriction, and electrophoresis. Main Outcome Measure(s): The ER Genotypes were classified into A through T (TA repeats, 10-29). The CYP17 genotypes included indigestible (A1 homozygote), heterozygote, and digestible (A2, homozygote). We compared these polymorphism distributions in both groups. Result(s): The percentage of genotypes D-G (TA, 13-16) in both groups were 110.5%, 29.4%, 13.0%, and 11.3% in group 1 and 7.9%, 16.7% 19.9%, and 17.6% in group 2. The genotype E (14 TA repeats) is associated with a higher risk of endometriosis. Proportions of Al homozygote/heterozygote/A2 homozygote for CYP17 were 26.1%/46.2%/27.7% for Group I and 14.8%/44.5%/40.7% for group 2, respectively. The Al homozygote and allele were associated with a higher susceptibility of endornetriosis. Conclusion(s): ER alpha* 14 TA repeats and the CYP17* Al allele are associated with an increased risk of endometriosis. Both polymorphisms are useful markers for predicting endometriosis susceptibility. (Fertil Steril (R) 2005:83:567-72. (c) 2005 by American Society for Reproductive Medicine.)