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 PopulationReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Gustavo Martelli-Palomino, Joao A. Pancotto, Yara C. Muniz, Celso T. Mendes-Junior, Erick C. Castelli, Juliana D. Massaro, Irene

Fuente: http://plos.srce.hr/



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