Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage

Hum Immunol. 2010 May;71(5):482-8. doi: 10.1016/j.humimm.2010.02.001. Epub 2010 Feb 19.


A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was significantly increased in probands with RM (p = 0.05). The increased compatibility between probands and their mothers for maternal G14 ins positive haplotypes suggests that maternal-fetal compatibility for chromosomal segments adjacent to HLA-G locus is a risk factor for female offspring to experience RM in their later reproductive life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • HLA Antigens / genetics*
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • HLA-G Antigens
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Linkage Disequilibrium
  • Pedigree
  • Pregnancy


  • HLA Antigens
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-G Antigens
  • Histocompatibility Antigens Class I