Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage

Objective: Proinflammatory cytokines have been described as etiologic factors in idiopathic recurrent miscarriage. We investigated the relation between idiopathic recurrent miscarriage and polymorphisms in the gene encoding for the interleukin 1 receptor antagonist, an indigenous modulator of proinflammatory immune response. Design: Prospective case control study. Setting: Academic research institution. Patient(s): One hundred five women with a history of three or more consecutive pregnancy losses before 20 weeks of gestation and 91 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Polymerase chain reaction was performed to identify the different alleles of the gene encoding for interleukin 1 receptor antagonist. Result(s): Allele frequencies among women with idiopathic recurrent miscarriage and controls were 0.34 and 0.11, respectively, for the polymorphic allele 2 (P=.002: odds ratio: 7.4, confidence interval: 2.9-10.8) and .05 and .05, respectively, for the polymorphic allele 3 (P=.6; odds ratio: 1.3, confidence interval: 0.8-2.3). Allele 2 was present in homozygous form in 9% of women with idiopathic recurrent miscarriage. In contrast, 1% of the control women were homozygous for this allele (P<.001; odds ratio: 13.5, confidence interval: 7.5-21.8). Conclusion(s): These data support a role for allele 2 of the gene encoding for interleukin I receptor antagonist as genetic determinant of idiopathic recurrent miscarriage. <(c)> 2001 by American Society for Reproductive Medicine.