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.
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.
Hviid
Thomas Vauvert F
TV
Department of Clinical Biochemistry, Roskilde University Hospital, Roskilde, Denmark.
Rizzo
Roberta
R
Melchiorri
Loredana
L
Stignani
Marina
M
Baricordi
Olavio R
OR
D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D015870:Gene Expression; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D015810:Linkage Disequilibrium; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*
D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D016753:Interleukin-10