TY - JOUR
T1 - Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus
AU - de Albuquerque, Rafael S.
AU - Mendes-Junior, Celso Teixeira
AU - Lucena-Silva, Norma
AU - da Silva, Camila Leal Lopes
AU - Rassi, Diane Meire
AU - Veiga-Castelli, Luciana C.
AU - Foss-Freitas, Maria Cristina
AU - Foss, Milton César
AU - Deghaide, Neifi Hassan Saloum
AU - Moreau, Philippe
AU - Gregori, Silvia
AU - Castelli, Erick C.
AU - Donadi, Eduardo Antônio
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G.
AB - Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G.
KW - 3' untranslated region
KW - Brazilians
KW - Gene regulation
KW - HLA-G
KW - Type 1 diabetes mellitus
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U2 - 10.1016/j.humimm.2016.02.001
DO - 10.1016/j.humimm.2016.02.001
M3 - Article
AN - SCOPUS:84959228474
VL - 77
SP - 358
EP - 364
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 4
ER -