ISSN: 0034-8376
eISSN: 2564-8896
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Abstract

HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes

VOLUME 68 - NUMBER 3 / May - June (Original articles)

Rita A. Gómez-Díaz, Department of Medical Investigation in Clinical Epidemiology, UMAE Hospital de Especialidades, Mexico City, Mexico; School of Medicine, Instituto Politécnico Nacional, Mexico City, Mexico
Elisa Nishimura-Meguro, Department of Endocrinology, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
Eulalia Garrido-Magaña, Department of Endocrinology, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
Lorena Lizárraga Paulin, Department of Pediatric Endocrinology, UMAE Hospital General Dr. Gaudencio González Garza, Mexico City, Mexico
Blanca E. Aguilar Herrera, Department of Pediatric Endocrinology, UMAE Hospital General Dr. Gaudencio González Garza, Mexico City, Mexico
Carolina Bekker-Méndez, Department of Medical Investigation in Infectology and Immunology, Hospital de Infectología, Centro Médico Nacional La Raza, IMSS, Mexico City, Mexico
Roberto Medina Santillán, School of Medicine, Instituto Politécnico Nacional, Mexico City, Mexico
Rodrigo Barquera, Laboratory of Physiology, Biochemistry and Genetics, Escuela Nacional de Antropología e Historia; Department of Immunogenetics and Human Identification, Laboratorios Diagnomol, Mexico City, Mexico
Rafael Mondragón-González, Department of Medical Investigation in Clinical Epidemiology, UMAE Hospital de Especialidades, Mexico City, Mexico; School of Medicine, Instituto Politécnico Nacional, Mexico City, Mexico
Niels H. Wacher, Department of Medical Investigation in Clinical Epidemiology, UMAE Hospital de Especialidades, Mexico City, Mexico; School of Medicine, Instituto Politécnico Nacional, Mexico City, Mexico

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*03:02, together with specific β-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 β-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 β-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*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, 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*03:02 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.

Keywords: HLA. Proinsulin. C-peptide. Mexican. Antibody.

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