Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage

Objective: Proinflammatory cytokines have been described as etiologic facto rs in idiopathic recurrent miscarriage. We investigated the relation betwee n idiopathic recurrent miscarriage and polymorphisms in the gene encoding f or the interleukin 1 receptor antagonist, an indigenous modulator of proinf lammatory immune response. Design: Prospective case control study. Setting: Academic research institution. Patient(s): One hundred five women with a history of three or more consecut ive pregnancy losses before 20 weeks of gestation and 91 healthy, postmenop ausal controls with at least two live births and no history of pregnancy lo ss. Intervention(s): Peripheral venous puncture. Main Outcome Measure(s): Polymerase chain reaction was performed to identif y the different alleles of the gene encoding for interleukin 1 receptor ant agonist. Result(s): Allele frequencies among women with idiopathic recurrent miscarr iage and controls were 0.34 and 0.11, respectively, for the polymorphic all ele 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, con fidence interval: 0.8-2.3). Allele 2 was present in homozygous form in 9% o f women with idiopathic recurrent miscarriage. In contrast, 1% of the contr ol women were homozygous for this allele (P<.001; odds ratio: 13.5, confide nce 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 Medi cine.