Human Immunology

Volume 77, Issue 12, December 2016, Pages 1179-1186

Author links open overlay panelCynthia HernandesCostaM.D.aGeorgia FernandaGelminiM.D.aFabiola SilvaNardiM.D.aValéria Maria Munhoz SperandioRoxoPh.D.aAlessandroSchuffner(Dr.)bMariada Graça BicalhoPh.D.a

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HLA-G codes for a non-classical class I (Ib) protein which is mainly expressed in trophoblast cells. Many pieces of evidence pointed out its essential role conferring immunological tolerance to the fetus. Some HLA-G alleles have been linked to enhanced or reduced HLA-G protein levels expression, which have been associated with reproductive failure. In this study 33 couples undergoing ART (assisted reproduction treatment; n = 66) and 120 couples who conceived naturally (controls; n = 240) were enrolled in the study. Genotyping was performed by SBT and tagged an 1837 bp at 5′URR as well as exons 2, 3 and 4 of HLA-G. Alleles, genotypes and haplotypes were compared between infertile and control groups using Fisher Exact Test. The haplotype HLA-G010101b/HLA-G01:01:01 showed statistically significant higher frequency in control groups. The immunogenetics of infertility is complex and might be dependent on different genes involved in the establishment of a successful pregnancy. A better understanding of HLA-G alleles and haplotypes structure and how the genetic diversity at their regulatory sites could impact on their level of expression and build up the susceptibility or protection conditions may shed light on the comprehension of immunogenetics mechanisms acting at the fetus-maternal interface.


HLA-G regulatory region

HLA-G coding region

Human reproduction

Protective haplotype

Susceptibility haplotype



assisted reproduction treatments


soluble HLA-G


single nucleotide polymorphism