Abstract

Recurrent miscarriage (RM) is the occurrence of repeated pregnancies that end in miscarriage of the fetus before 20 weeks of gestation. At least 50% of the RM patients are considered idiopathic. High IL-33 levels are critical in early pregnancy and impact the outcome of subsequent pregnancies. However, the association of polymorphisms of IL-33 with idiopathic RM is still unclear. The present study was initiated to investigate whether IL-33 polymorphisms are risk factors for idiopathic RM in Chinese Han population. Study subjects comprised of 321 cases and 384 controls. Five polymorphisms (rs10435816, rs16924159, rs16924171, rs1929992, rs1332290) in IL-33 and serum IL-33 concentrations were assessed. rs16924159 variant exhibits significant association with RM in additive and recessive genetic model (additive model P = 0.015, recessive model P = 0.007). In contrast, rs10435816, rs16924171, rs1929992 and rs1332290 are not significantly associated with RM. Serum IL-33 levels are significantly lower in RM cases than in control (173.51 ± 94.12 versus. 200.97 ± 110.06 (pg/ml), P = 4.57 × 10−4). There are lower levels of serum IL-33 in rs16924159 homozygous mutant (AA) than homozygous wild-type (GG) in this study population, including cases and control groups (172.18 ± 103.01 versus. 205.82 ± 119.01 (pg/ml), P = 0.006). Reduced IL-33 levels and rs16924159 IL-33 variant may contribute to the pathogenesis of idiopathic RM in Chinese Han population.

Highlights

  • In contrast to the Tregs cells, the proportion of Th17 cells was significantly higher in patients with Recurrent miscarriage (RM) than in normal pregnant[11–13]

  • The role of IL-33 polymorphisms in idiopathic RM pathogenesis remains unknown. In this case–control study, we selected five tag SNPs in IL-33 to investigate the association of IL-33 polymorphisms with idiopathic RM

  • We found that a tag SNP rs16924159, located in the regulatory region of IL-33, was associated with idiopathic RM

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Summary

Introduction

In contrast to the Tregs cells, the proportion of Th17 cells was significantly higher in patients with RM than in normal pregnant[11–13]. Sequential activation of the IL-33/ST2L/sST2 axis was disordered in decidualizing HESCs from women with recurrent pregnancy loss. There is a significant increase in serum IL-33 levels from patients who went on to abortion compared with normal control pregnancies[24]. The association of polymorphisms of IL-33 with idiopathic RM is still unclear. The present study was initiated to evaluate association of the IL-33 gene polymorphisms with idiopathic RM in Chinese Han population. Five polymorphisms (rs10435816, rs16924159, rs16924171, rs1929992, rs1332290) in IL-33 gene were selected for genotyping, and we analyzed the association between the five SNPs and the risk of idiopathic RM

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