HLA‐G 3′‐UTR SNP and 14‐bp deletion polymorphisms in Portuguese and Guinea‐Bissau populations

Abstract

In the HLA-G locus, the 3'-untranslated region (3'-UTR) begins in the mid exon 6, and ends in exon 8. The occurrence of a 14-bp deletion within exon 8, the only mutation known until now in the 3'-UTR, has been considered a risk factor for disease and allograft rejection. To describe the polymorphism within this region, direct sequencing analysis was performed on 120 DNA samples from Portugal and Guinea-Bissau. Results indicate that exon 8 is less conserved than the coding exons. Nine single nucleotide polymorphisms and the previously described 14-bp deletion were found within exon 8 of both populations. Molecular diversity was higher in the Guinean samples than in the Portuguese; however, little differentiation was found among the populations, suggesting that local selection on exon 8 sequence variation is absent. The screening for sequence motifs suggests that polymorphism on this region may be involved in HLA-G post-transcriptional regulation and, therefore, in phenotype variation.

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

“…These frequencies are also similar to those reported for Southeastern (41%) [12], Southern (39.5%) [47], Northeastern (37%) [44], and Native American (38.4%) [48] Brazilians. Quite closer frequencies were observed for Italian (38%) [49], German (38%) [50] and Portuguese (47%) [51] healthy individuals. Although the frequencies of the 14-bp Ins/Del genotypes were quite similar for Brazilian and French individuals, in Brazilians they may vary on a regional basis.…”

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

“…7,[9][10][11][12][13][14] HLA-G 3′UTR nucleotide variations have been extensively studied in both experimental and pathological conditions, and several of these polymorphic sites have been shown to influence HLA-G production by modifying the binding of specific microRNAs or the stability of the HLA-G mRNA. [15][16][17] Notably, the 14-bp insertion/deletion (indel, rs371194629) has been associated with a wide range of clinical conditions, including transplantation, tumors, pregnancy disorders, autoimmune diseases and chronic viral infections.…”

HLA-G expression levels influence the tolerogenic activity of human DC-10

“…15 These polymorphisms cluster in at least 15 different haplotypes identified in Brazilian populations, 13,16 and a number of less frequent haplotypes found in other populations. 17,18 The functions of HLA-G are oriented towards immune inhibition and induction of tolerance. Through direct binding to the inhibitory receptors Immunoglobulin-Like-Transcript (ILT)2 and ILT4, and Killer cell Immunoglobulin-Like Receptor (KIR)2DL4, 19 HLA-G mediates short-term inhibition of natural killer (NK) cells, 20 cytotoxic T-lymphocytes, 21 B cells, 22 and dendritic cells (DC) 23,24 and long-term induction of regulatory cells including HLA-G-expressing T regulatory (Treg) cells, 23 Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions.…”