title: Polymorphic sites at the 3' untranslated region of the HLA-G gene are associated with differential hla-g soluble levels in the Brazilian and French population.
abstract: HLA-G molecule has well-recognized tolerogenic properties, and the encoding gene shows lower frequency of polymorphism at the coding region but higher variability at regulatory 5' and 3' untranslated (3'UTR) regions. At least three 3'UTR polymorphic sites have been associated with HLA-G mRNA regulation, including the 14 base pair (14bp) Insertion/Deletion, +3142C-G and +3187A-G. We studied the association of polymorphic sites at 3'UTR (sequencing analysis, encompassing the 14bp Ins-Del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G polymorphic sites) with plasma soluble HLA-G levels (sHLA-G, detected by ELISA) in 187 French and 153 Brazilian healthy individuals. Allele and genotype frequencies were closely similar in both populations; however, Brazilians showed a higher HLA-G 3'UTR haplotype diversity. Considering sHLA-G levels in both populations altogether, individuals presenting 14bp Del/Del showed higher levels compared to 14bpIns/Ins genotype (P <0.05); those presenting +3010C/G showed higher levels compared to the +3010C-C genotype (P< 0.05); those presenting +3027C-C showed higher levels than the +3027A-A genotype (P< 0.05); and those bearing +3035C-C showed higher levels compared to the +3035C-T (P < 0.01) and +3035T-T (P < 0.05) genotypes. The analyses of 3'UTR haplotypes showed that UTR-1 (DelTGCCCGC) was associated with higher expression of sHLA-G, whereas UTR-5 (InsTCCTGAC) and UTR-7 (InsTCATGAC) with lower expression and other UTRs (UTR-2/3/4/6) exhibited intermediate levels. Since the differential expression of HLA-G may be beneficial or harmful depending on the underlying condition, the identification of individuals genetically programmed to differentially express HLA-G may help on defining novel strategies to control the immune response against the underlying disorder.
authors.affiliation: Program of Basic and Applied Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil ; Commissariat à l'energie atomique et aux energies alternatives, institut des maladies emergentes et des therapies innovantes, service de recherches en hemato-immunologie, Hôpital Saint-Louis, Paris, France ; Universite Paris-Diderot, sorbonne paris-cite, umr-e5, institut universitaire d'hematologie, Hopital Saint-Louis, Paris, France.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli-Palomino
authors.forename: Joao A
authors.initials: JA
authors.lastname: Pancotto
authors.forename: Yara C
authors.initials: YC
authors.lastname: Muniz
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Massaro
authors.forename: Irene
authors.initials: I
authors.lastname: Krawice-Radanne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poras
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D017398:Alternative Splicing; D001938:Brazil; D005260:Female; D005602:France; D005787:Gene Frequency; D005838:Genotype; D059951:HLA-G Antigens / Q000097:blood* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; D020033:Protein Isoforms