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HLA-G UTR haplotype conservation in the Malian population: association with soluble HLA-G.

  • Carlini F Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
  • Traore K Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, Bamako, Mali.
  • Cherouat N Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
  • Roubertoux P Inserm U491, Génétique Médicale et Développement, Aix-Marseille Université, Faculté de Médecine, Marseille, France.
  • Buhler S Laboratory of Anthropology, Genetics and Peopling history (AGP), Department of Genetics and Evolution - Anthropology Unit, University of Geneva, Geneva, Switzerland.
  • Cortey M Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
  • Simon S Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
  • Doumbo O Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, Bamako, Mali.
  • Chiaroni J Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
  • Picard C Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France ; Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
  • Di Cristofaro J Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
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  • 2013-12-31
Published in:
  • PloS one. - 2013
3' Untranslated Regions
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Child
Child, Preschool
Conserved Sequence
Female
Gene Frequency
Genetic Loci
HLA-A Antigens
HLA-G Antigens
Haplotypes
Humans
Linkage Disequilibrium
Male
Mali
Middle Aged
Polymorphism, Single Nucleotide
Solubility
Young Adult
English The HLA-G molecule plays an important role in immunomodulation. In a previous study carried out on a southern French population our team showed that HLA-G haplotypes, defined by SNPs in the coding region and specific SNPs located in 5'URR and 3'UTR regulatory regions, are associated with differential soluble HLA-G expression (sHLA-G). Furthermore, the structure of these HLA-G haplotypes appears to be conserved in geographically distant populations. The aim of our study is to confirm these expectations in a sub-Saharan African population and to explore additional factors, such as HLA-A alleles, that might influence sHLA-G expression. DNA and plasma samples were collected from 229 Malians; HLA-G and HLA-A genotyping were respectively performed by the Snap Shot® method and by Luminex™ technology. sHLA-G dosage was performed using an ELISA kit. HLA-G and HLA-A allelic and haplotypic frequencies were estimated using an EM algorithm from the Gene[Rate] program. Associations between genetic and non genetic parameters with sHLA-G were performed using a non-parametric test with GRAPH PAD Prism 5. Our results reveal a good conservation of the HLA-G UTR haplotype structure in populations with different origins and demographic histories. These UTR haplotypes appear to be involved in different sHLA-G expression patterns. Specifically, the UTR-2 haplotype was associated with low sHLA-G levels, displaying a dominant negative effect. Furthermore, an allelic effect of both HLA-G and HLA-A, as well as non genetic parameters, such as age and gender possibly linked to osteogenesis and sexual hormones, also seem to be involved in the modulation of sHLA-G. These data suggest that further investigation in larger cohorts and in populations from various ethnical backgrounds is necessary not only to detect new functional polymorphism in HLA-G regulatory regions, but also to reveal the extent of biological phenomena that influence sHLA-G secretion and this might therefore have an impact on transplantation practice.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/254882
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