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High mobility group box 1 protein polymorphism affects susceptibility to recurrent pregnancy loss by up-regulating gene expression in chorionic villi

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Inflammation in chorionic villi is involved in the development of recurrent pregnancy loss (RPL). High mobility group box 1 protein (HMGB1) plays critical roles in inflammation and expression of the protein can be found in chorionic villi. The purpose of the study was to investigate the association between HMGB1 genetic polymorphisms and susceptibility to RPL and to examine the mechanism underlying this correlation.

Methods

Two HMGB1 polymorphisms, rs2249825C/G and rs1412125T/C, were examined in 112 RPL patients and 118 healthy controls by the polymerase chain reaction–restriction fragment length polymorphism assay.

Results

Percentage of rs2249825GG was significantly increased in patients than in controls (Odd ratio [OR] =2.33, 95 % confidence interval [CI]: 1.18–4.58, P = 0.013). Also, prevalence of rs2249825G allele was significantly higher in RPL cases (OR = 1.77, 95 % CI: 1.20–2.62, P = 0.004). Function analysis of rs2249825C/G revealed that the polymorphism did not affect serum level of HMGB1. Interestingly, we found significantly increased level of HMGB1 in chorionic villi from RPL patients. Moreover, patients with rs2249825GG genotype presented significantly elevated level of HMGB1 in chorionic villi compared to those with CG or CC genotypes.

Conclusions

These results suggest that HMGB1 rs2249825C/G polymorphism is associated with increased risk of RPL and can elevate gene expression in chorionic villi.

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Acknowledgments

This work was supported by Jinan Science and Technology Bureau Grant Award (201112003). Title: “The clinical application study for first-trimester villi prenatal diagnosis”.

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None.

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Authors

Corresponding author

Correspondence to Cuiying Liu.

Additional information

Capsule Inflammation in chorionic villi may play critical roles in the development of recurrent pregnancy loss (RPL). Here, we identified an association between HMGB1 rs2249825 C/G SNP and increased risk of RPL. Moreover, RPL patients carrying rs2249825 GG genotype revealed increased level of HMGB1 in the chorionic villi than those with CC and CG genotypes. These data suggest that HMGB1 rs2249825C/G polymorphism may affect susceptibility to RPL by up-regulating gene expression in chorionic villi.

Hua Jin and Jie Wu contributed equally to this work.

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Jin, H., Wu, J., Yang, Q. et al. High mobility group box 1 protein polymorphism affects susceptibility to recurrent pregnancy loss by up-regulating gene expression in chorionic villi. J Assist Reprod Genet 32, 1123–1128 (2015). https://doi.org/10.1007/s10815-015-0493-3

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  • DOI: https://doi.org/10.1007/s10815-015-0493-3

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