1. Classical HLA alleles tag SNP in families from Antioquia with type 1 diabetes mellitus
- Author
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Sarrazola DC, Rodríguez AM, Toro M, Vélez A, García-Ramírez J, Lopera MV, Álvarez CM, González VB, Alfaro JM, and Pineda-Trujillo N
- Subjects
- Adult, Alleles, CTLA-4 Antigen genetics, Colombia epidemiology, Computer Simulation, Diabetes Mellitus, Type 1 epidemiology, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genotype, Humans, Interferon-Induced Helicase, IFIH1 genetics, Linkage Disequilibrium, Male, Models, Genetic, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics, Diabetes Mellitus, Type 1 genetics, Genes, MHC Class I, Genes, MHC Class II, HLA Antigens genetics, Polymorphism, Single Nucleotide
- Abstract
Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.
- Published
- 2018
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