The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes.
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.
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
H P V
HP
Silva
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
M A G
MA
Ururahy
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
K S C
KS
Souza
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
M B
MB
Loureiro
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
Y M C
YM
Oliveira
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
G H M
GH
Oliveira
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
A D
AD
Luchessi
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
K T C
KT
Carvalho
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
J C O C
JC
Freitas
Department of Clinical and Toxicological Analyses, University of Sao Paulo, Sao Paulo, Brazil.
E A
EA
Donadi
Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
R D C
RD
Hirata
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
M G
MG
Almeida
Pediatrics Endocrinology Unit, Federal University of Rio Grande do Norte, Natal, Brazil.
R F
RF
Arrais
Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
M H
MH
Hirata
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
A A
AA
Rezende
D000293:Adolescent; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic
D006681:HLA-D Antigens; D059951:HLA-G Antigens