The nonclassical human leukocyte antigen (HLA) class Ib gene HLA-G may be important for the induction and maintenance of immune tolerance between the mother and the semi-allogeneic fetus during pregnancy. Expression of HLA-G can influence cytokine and cytotoxic T-lymphocyte responses. Different HLA-G mRNA isoform expression patterns have been associated with HLA-G polymorphism, especially with a 14-bp insertion deletion polymorphism in the 3′ untranslated region (3′UTR) of the HLA-G gene. A significantly high level of interleukin-10 (IL-10) secretion is observed in homozygous +14/+14-bp HLA-G peripheral blood mononuclear cells after lipopolysaccharide (LPS) stimulation. This study finds that polymorphism in the 5′ upstream regulatory region (5′URR) of the HLA-G gene may also be implicated in differences in IL-10 secretion. However, this may also be due to linkage disequilibrium with the 14-bp polymorphism. A single-nucleotide polymorphism located −477 bp from the start site of exon 1 had a significant association with IL-10 concentrations but not after correction (p = 0.011; pc = 0.154). This polymorphism is located next to a heat shock element. Eighteen 5′-URR/3′-UTR HLA-G haplotypes were defined; one common homozygous genotype based on these haplotypes was significantly associated with a high IL-10 level after LPS stimulation compared to certain other genotypes. This study indicates that polymorphism in the 5′-URR of the HLA-G gene may have functional significance, although a new line of investigations is needed to elucidate these findings.

Polymorphism in the 5' upstream regulatory and 3' untranslated regions of the HLA-G gene in relation to soluble HLA-G and IL-10 expression

RIZZO, Roberta;STIGNANI, Marina;BARICORDI, Olavio
2006

Abstract

The nonclassical human leukocyte antigen (HLA) class Ib gene HLA-G may be important for the induction and maintenance of immune tolerance between the mother and the semi-allogeneic fetus during pregnancy. Expression of HLA-G can influence cytokine and cytotoxic T-lymphocyte responses. Different HLA-G mRNA isoform expression patterns have been associated with HLA-G polymorphism, especially with a 14-bp insertion deletion polymorphism in the 3′ untranslated region (3′UTR) of the HLA-G gene. A significantly high level of interleukin-10 (IL-10) secretion is observed in homozygous +14/+14-bp HLA-G peripheral blood mononuclear cells after lipopolysaccharide (LPS) stimulation. This study finds that polymorphism in the 5′ upstream regulatory region (5′URR) of the HLA-G gene may also be implicated in differences in IL-10 secretion. However, this may also be due to linkage disequilibrium with the 14-bp polymorphism. A single-nucleotide polymorphism located −477 bp from the start site of exon 1 had a significant association with IL-10 concentrations but not after correction (p = 0.011; pc = 0.154). This polymorphism is located next to a heat shock element. Eighteen 5′-URR/3′-UTR HLA-G haplotypes were defined; one common homozygous genotype based on these haplotypes was significantly associated with a high IL-10 level after LPS stimulation compared to certain other genotypes. This study indicates that polymorphism in the 5′-URR of the HLA-G gene may have functional significance, although a new line of investigations is needed to elucidate these findings.
2006
Hviid, T. V. F.; Rizzo, Roberta; Melchiorri, L.; Stignani, Marina; Baricordi, Olavio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1209698
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