HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes.
Rev Invest Clin
; 68(3): 128-36, 2016.
Article
em En
| MEDLINE
| ID: mdl-27408999
ABSTRACT
BACKGROUND:
Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*0302, together with specific ß-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes.OBJECTIVE:
To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with ß-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls.METHODS:
We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and ß-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data.RESULTS:
We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*0302 in 95.7% of patients vs. 51.87% of controls; DRB1*0301/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*0301 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*0302, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype.CONCLUSIONS:
The DRB1*04/DQA1*03/DQB1*0302 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Antígenos HLA-D
/
Diabetes Mellitus Tipo 1
/
Insulina
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Mexico
Idioma:
En
Revista:
Rev Invest Clin
Assunto da revista:
MEDICINA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
México