Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus

Human Immunology
R S de AlbuquerqueEduardo A Donadi

Abstract

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 ...Continue Reading

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Citations

Sep 22, 2016·Journal of Immunology Research·Fabio MorandiVito Pistoia
May 28, 2019·Expert Review of Endocrinology & Metabolism·Linda SommeseClaudio Napoli
Oct 2, 2020·International Journal of Immunogenetics·Antonio Arnaiz-VillenaJose M Martin-Villa
Aug 1, 2020·Frontiers in Immunology·Giada Amodio, Silvia Gregori
Jun 11, 2021·International Journal of Immunogenetics·Christine NeuchelJoannis Mytilineos
Jan 15, 2022·Medicine·Natalia Alves CorteletteJoão Alexandre Trés Pancoto

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