TY - JOUR
T1 - 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
AU - Hviid, Thomas Vauvert F.
AU - Rizzo, Roberta
AU - Melchiorri, Loredana
AU - Stignani, Marina
AU - Baricordi, Olavio R.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
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.
KW - 3′UTR
KW - HLA-G
KW - Regulatory region
KW - sHLA-G
UR - http://www.scopus.com/inward/record.url?scp=33646347407&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2005.12.003
DO - 10.1016/j.humimm.2005.12.003
M3 - Article
C2 - 16698426
AN - SCOPUS:33646347407
SN - 0198-8859
VL - 67
SP - 53
EP - 62
JO - Human Immunology
JF - Human Immunology
IS - 1-2
ER -