HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

Immunogenetics. 2003 May;55(2):63-79. doi: 10.1007/s00251-003-0547-z. Epub 2003 Apr 24.


During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a significantly lower level than the corresponding HLA-G mRNA isoforms with the 14-bp sequence deleted. Furthermore, characteristic HLA-G mRNA isoform expression patterns were associated with specific HLA-G genotypes and alleles. In the HLA-G*01012 and - G*01013 alleles that include the 14-bp sequence, an additional alternative splicing was observed, with the first 92-bp of exon 8 spliced out. This was most pronounced in HLA-G genotypes with G*01013. These findings may have functional implications for the recent reports of aberrant HLA-G expression and reproductive success.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Gene Expression Profiling
  • Genetic Variation
  • HLA Antigens / genetics*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trophoblasts / metabolism


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • RNA, Messenger