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

Rafael S. de Albuquerque, Celso Teixeira Mendes-Junior, Norma Lucena-Silva, Camila Leal Lopes da Silva, Diane Meire Rassi, Luciana C. Veiga-Castelli, Maria Cristina Foss-Freitas, Milton César Foss, Neifi Hassan Saloum Deghaide, Philippe Moreau, Silvia Gregori, Erick C. Castelli, Eduardo Antônio Donadi

Research output: Contribution to journalArticle

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 in individuals genetically prone to produce less HLA-G.

Original languageEnglish
Pages (from-to)358-364
Number of pages7
JournalHuman Immunology
Volume77
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Keywords

  • 3' untranslated region
  • Brazilians
  • Gene regulation
  • HLA-G
  • Type 1 diabetes mellitus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

de Albuquerque, R. S., Mendes-Junior, C. T., Lucena-Silva, N., da Silva, C. L. L., Rassi, D. M., Veiga-Castelli, L. C., Foss-Freitas, M. C., Foss, M. C., Deghaide, N. H. S., Moreau, P., Gregori, S., Castelli, E. C., & Donadi, E. A. (2016). Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus. Human Immunology, 77(4), 358-364. https://doi.org/10.1016/j.humimm.2016.02.001