Interleukin–1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage

Abstract

Objective: To investigate the relationship between idiopathic recurrent miscarriage (IRM) and two polymorphisms of intron 2 of the gene-encoding interleukin–1 receptor antagonist, an autochthonous modulator of the proinflammatory immune response. Materials and Methods: 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 were investigated. Polymerase chain reaction was performed to identify the wild-type allele (allele 1) and two polymorphic alleles (alleles 2 and 3) of the interleukin–1 receptor antagonist gene. Results: Allele frequencies among women with IRM and controls were 0.34 and 0.11, respectively, for allele 2 ( P = 0.002; odds ratio: 7.4, confidence interval: 2.9–10.8) and 0.05 and 0.05, respectively, for allele 3 ( P = 0.6; odds ratio: 1.3, confidence interval: 0.8–2.3). Allele 2 was present in homozygous form ( IL–1 RA 2/2 ) in 9% of women with IRM. In contrast, 1% of the control women were homozygous for this allele ( P <0.001; odds ratio: 13.5, confidence interval: 7.5–21.8). Between women with primary and secondary recurrent miscarriages, no statistically significant differences with respect to frequencies of allele 2 genotypes IL–1 RA 1/2 (23% versus 26%, P = 0.2) and IL–1 RA 2/2 (8% versus 10%, P = 0.1) were observed. Conclusion: These data support a role for allele 2 of the interleukin–1 receptor antagonist gene as genetic determinant of IRM.