title: High mobility group box 1 protein polymorphism affects susceptibility to recurrent pregnancy loss by up-regulating gene expression in chorionic villi.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Prenatal Diagnosis, The Maternal and Child Health Hospital of Jinan City, Jinan City, Shandong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Wenxiu
authors.initials: W
authors.lastname: He
authors.forename: Cuiying
authors.initials: C
authors.lastname: Liu
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D002824:Chorionic Villi / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human