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

Abstract

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.

14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

“…The HLA-G 3´-UTR contains regulatory elements included polyadenylation signals and AU-rich sequences (Castelli et al, 2010), which play important role in the spatial and temporal expression of HLA-G (Gonzalez et al, 2012). Therefore, the different polymorphisms located in the HLA-G 3´-UTR can influence the HLA-G expression.…”

Analysis of HLA-G gene polymorphisms in Slovak women with pre-eclampsia

“…The +3142 polymorphism is a target for certain miRNAs that are responsible for degrading HLA-G mRNA. Furthermore, the +3187 and the +3196 SNPs are located just before and after an AUUUA motif associated with mRNA stability (11).…”

“…HLA-G gene is characterized by low polymorphism, namely 53 HLA-G alleles, 18 HLA-G proteins and 2 null alleles have been identifi ed until now (IMGT/HLA database, January 2017). The most polymorphic sites that infl uence HLA-G expression were identifi ed in the 5′ and 3′ non-coding regions (10,11). In the 3′ UTR, the 14 bp insertion polymorphism (5′-ATTTGTTCATGCCT-3′) was described, that affects stability of mRNA causing a lower production of most membrane and soluble isoforms (10).…”

Untitled

“…10 The HLA-G gene is located within the major histocompatibility complex at the telomeric part of the 6p21.3 chromosomal region and has few polymorphisms compared with other genes located in this region. 11 In healthy subjects, HLA-G is expressed in few tissues such as extravillous cytotrophoblasts, oocytes, embryos, amnion, and thymic epithelial cells. 3 In patients who have transplant, cancer, viral infection, multiple sclerosis, or inflammatory diseases, the HLA-G molecule may be induced in tissues affected by disease.…”