PMID- 16698426 OWN - NLM STAT- MEDLINE DCOM- 20060829 LR - 20111117 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 67 IP - 1-2 DP - 2006 Jan-Feb TI - 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. PG - 53-62 AB - 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. FAU - Hviid, Thomas Vauvert F AU - Hviid TV AD - Department of Clinical Biochemistry, Roskilde University Hospital, Roskilde, Denmark. FAU - Rizzo, Roberta AU - Rizzo R FAU - Melchiorri, Loredana AU - Melchiorri L FAU - Stignani, Marina AU - Stignani M FAU - Baricordi, Olavio R AU - Baricordi OR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060331 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (3' Untranslated Regions) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Lipopolysaccharides) RN - 130068-27-8 (Interleukin-10) SB - IM MH - 3' Untranslated Regions/*genetics MH - Base Sequence MH - Gene Expression MH - HLA Antigens/*genetics MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/*genetics MH - Humans MH - Interleukin-10/*metabolism MH - Leukocytes, Mononuclear/drug effects/immunology MH - Linkage Disequilibrium MH - Lipopolysaccharides/pharmacology MH - Molecular Sequence Data MH - *Polymorphism, Genetic MH - Regulatory Elements, Transcriptional/*genetics EDAT- 2006/05/16 09:00 MHDA- 2006/08/30 09:00 CRDT- 2006/05/16 09:00 PHST- 2005/09/26 00:00 [received] PHST- 2006/05/16 09:00 [pubmed] PHST- 2006/08/30 09:00 [medline] PHST- 2006/05/16 09:00 [entrez] AID - S0198-8859(05)00468-4 [pii] AID - 10.1016/j.humimm.2005.12.003 [doi] PST - ppublish SO - Hum Immunol. 2006 Jan-Feb;67(1-2):53-62. doi: 10.1016/j.humimm.2005.12.003. Epub 2006 Mar 31.