HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage

Mol Hum Reprod. 2001 Dec;7(12):1167-72. doi: 10.1093/molehr/7.12.1167.


HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abortion, Habitual / genetics*
  • Abortion, Habitual / immunology
  • Adult
  • Alleles
  • Female
  • Genotype
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Pregnancy Outcome
  • Pregnancy*
  • Risk Factors
  • Treatment Outcome


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I