The PROGINS progesterone receptor gene polymorphism and idiopathic recurrent miscarriage

OBJECTIVE: Progesterone inhibits lymphocyte cytotoxicity, natural killer ce ll degranulation, and release of proinflammatory cytokines and has been sho wn to protect against spontaneous miscarriage. We investigated the associat ion between idiopathic recurrent miscarriage (IRM) and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor gene, which is known to segregate with progesterone-dependent neoplasms. METHODS: In a case-control study we investigated 125 women with a history o f three or more consecutive pregnancy losses before 20 weeks' gestation and 79 healthy controls with at least two live births and no history of pregna ncy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction were used to genotype women for the presence of the PROGINS polymo rphism. RESULTS: Allele frequencies among women with IRM and controls were 85.2% an d 89.2%, respectively, for allele T1 (wild type) and 14.8% and 10.8%, respe ctively, for allele T2 (mutant). No association between allele T2 and the o ccurrence of IRM was found (P = .3; odds ratio [OR] 0.69; confidence interv al [CI] 0.34, 1.40). Genotype frequencies were not significantly different between the study group (T1/T1 73.6%, T1/T2 23.2%, T2/T2 3.2%) and the cont rol group (T1/T1 79.7%, T1/T2 19%, T2/T2 1.3%) (P = .4). Between women with primary and secondary IRM, there were no statistically significant differe nces with respect to allele frequencies (82% versus 87%, P = .4 for allele T1 and 12% versus 13%, P = .6 for allele T2). CONCLUSIONS: We found that the PROGINS polymorphism in the progesterone rec eptor gene was not associated with IRM in white women. Copyright (C) 2001 b y the Society for Gynecologic Investigation.