The genetic structure of 3′untranslated region of the HLA-G gene: polymorphisms and haplotypes

• Published in: Genes and immunity Vol. 11; no. 2; pp. 134 - 141
• Main Authors: Castelli, E C, Mendes-Junior, C T, Deghaide, N H S, de Albuquerque, R S, Muniz, Y C N, Simões, R T, Carosella, E D, Moreau, P, Donadi, E A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2010; Nature Publishing Group
• Subjects: 3' Untranslated regions; Alleles; Antigens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cytotoxicity; Dendritic cells; Fetuses; Gene deletion; Gene Expression; Gene polymorphism; Genes; Genetic aspects; Genetic structure; Haplotypes; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; Human Genetics; Immunoglobulins; Immunological tolerance; Immunology; Insertion; Leukocytes; Linkage disequilibrium; Lupus; Lymphocytes; Lymphocytes T; Messenger RNA; MicroRNAs; mRNA; original-article; Physiological aspects; Polymorphism; Preeclampsia; Single nucleotide polymorphisms; Single-nucleotide polymorphism; T cells; Variation; Brazil; United States > US; microRNA; polymorphism; major histocompatibility complex; 3′untranslated region; HLA-G; human leukocyte antigens
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2009.74

The HLA-G gene is predominantly expressed at the maternal–fetal interface. It has been associated with maternal–fetal tolerance and in the inhibition of cytotoxic T lymphocyte and natural killer cytolytic functions. At least two variations in the 3′untranslated region (UTR) of HLA-G locus are associated with HLA-G expression levels, the 14-bp deletion/insertion polymorphism and the +3142 single-nucleotide polymorphism (SNP). However, this region has not been completely characterized yet. The variability of the 3′UTR of HLA-G gene and its haplotype structure were characterized in 155 individuals from Brazil, as well as HLA-G alleles associated with each of the 3′UTR haplotype. The following eight variation sites were detected: the 14-bp polymorphism and SNPs at the positions +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and +3196C/G. Similarly, 11 different 3′UTR haplotypes were identified and several HLA-G alleles presented only one 3′UTR haplotype. In addition, a high linkage disequilibrium among the variation sites was detected, especially among the 14-bp insertion and the alleles +3142G and +3187A, all previously associated with low mRNA availability, demonstrating that their effects are not independent. The detailed analyses of 3′UTR of the HLA-G locus may shed some light into mechanisms underlying the regulation of HLA-G expression.