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The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes

Genes & Immunity volume 17, pages 13–18 (2016)Cite this article

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Abstract

Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.

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Acknowledgements

This study was supported by CNPq research project (Grant number 620099/2008-9) and CAPES scholarship. We thank all of the volunteers who participated in this study. We are grateful for the technical support provided by students and technicians from LABMULT/UFRN/RN, LABIOMOL/UFRN/RN and FUNDHERP/SP in special to Neifi Hassan Saloum Deghaide. We also thank all of the physicians, nurses and hospital staff at HOSPED/UFRN who were involved in this study.

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Authors and Affiliations

  1. Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil

    H P V Silva, M A G Ururahy, K S C Souza, M B Loureiro, Y M C Oliveira, G H M Oliveira, A D Luchessi, K T C Carvalho, J C O C Freitas, M G Almeida & A A Rezende

  2. Department of Clinical and Toxicological Analyses, University of Sao Paulo, Sao Paulo, Brazil

    E A Donadi

  3. Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    R D C Hirata & M H Hirata

  4. Pediatrics Endocrinology Unit, Federal University of Rio Grande do Norte, Natal, Brazil

    R F Arrais

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Silva, H., Ururahy, M., Souza, K. et al. The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes. Genes Immun 17, 13–18 (2016). https://doi.org/10.1038/gene.2015.45

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