HLA-G in Amerindians: Epidemiology and Worldwide Population Comparison

Antonio Arnaiz-Villena*, Mercedes Enriquez-de-Salamanca$, Jose Palacio-Gruber, Ignacio Juarez, Ester Muñiz, Jorge Nieto, Cristina Campos, Jose Manuel Martin-Villa
Department of Immunology, University Complutense, School of Medicine, The Madrid Regional Blood Center, Madrid, Spain.

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Creative Commons License
© 2018 Arnaiz-Villena et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Immunology, University Complutense, School of Medicine, The Madrid Regional Blood Center, Madrid, Spain; Tel: +34 913941642/7080, +34 600993161; E-mail:; URL:
$ These authors contributed equally for this work and the order of authorship is arbitrary.



HLA-G molecules are immunosuppressive and avoid fetal rejection by giving negative signals to maternal immune system from fetal trophoblast cell surface. HLA-G genes have been associated to different pathologies: Spontaneous abortions, autoimmunity, tumor progression, transplant rejection and infection. In addition, different World populations show remarkable different HLA-G allele frequencies in the allele that does not produce a full HLA-G molecule (HLA-G*05N); this allele is almost absent in studied Amerindians.


The aim is to study HLA-A.-B,-DRB1 and –G alleles and extended haplotypes in Amerindians for the first time. This may be useful to asses HLA-G epidemiology, association to disease and Preventive Medicine in Amerindians.


HLA-A,-B and -DRB1 have been typed by using standard automatic protocols. HLA-G alleles have been detected by direct HLA-G exon 2, exon 3 and exon 4 DNA sequencing. Computer calculations have been done by specific standard methods.


HLA-A,-B,-DRB1 and –G extended haplotypes have been calculated in Amerindians for the first time. Also, their HLA-G frequencies have been compared with worldwide populations.


Low frequencies of null HLA-G*01:05N allele are found in Amerindians. The extended haplotypes with this allele bear other typical Amerindian HLA-DRB1 alleles and its origin is discussed. HLA-G allele frequency profile is closer to that of Europeans than to that of Far East Asians. Our findings are useful to Preventive Medicine and Epidemiology associated to Fertility and HLA-G associated pathology and transplantation.

Keywords: Abortion, Amerindians, Autoimmunity, Epidemiology, Fertility, HLA-G, HLA-G*01:20, HLA-G*01:08:02, Immune Suppression, Population Genetics, Transplantation, Tumor.