title: HLA-G UTR haplotype conservation in the Malian population: association with soluble HLA-G.
abstract: 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.
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Carlini
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, Bamako, Mali.
authors.forename: Karim
authors.initials: K
authors.lastname: Traore
authors.affiliation: Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
authors.forename: Nissem
authors.initials: N
authors.lastname: Cherouat
authors.affiliation: Inserm U491, Génétique Médicale et Développement, Aix-Marseille Université, Faculté de Médecine, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roubertoux
authors.affiliation: Laboratory of Anthropology, Genetics and Peopling history (AGP), Department of Genetics and Evolution - Anthropology Unit, University of Geneva, Geneva, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Buhler
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: Martì
authors.initials: M
authors.lastname: Cortey
authors.affiliation: Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Simon
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, Bamako, Mali.
authors.forename: Ogobara
authors.initials: O
authors.lastname: Doumbo
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France ; Immuno-genetics laboratory, Etablissement Français du Sang Alpes Méditerranée, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Picard
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Di Cristofaro
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D015234:HLA-A Antigens / Q000235:genetics; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008302:Mali; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012995:Solubility; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D015234:HLA-A Antigens; D059951:HLA-G Antigens