Relationship of type 1 diabetes to ancestral proportions and HLA DR/DQ alleles in a sample of the admixed Cuban population

• Published in: Annals of human biology 2010-11, Vol.37 (6), p.778-788
• Main Authors: Diaz-Horta, Oscar, Cintado, Alberto, Fernandez-De-Cossio, Maria Elena, Nazabal, Marcelo, Ferrer, Annia, Roca, Juan, Camacho, Hamlet, Benítez, Jesus, Ale, Mayte, Villarreal, Adelaida, Molina, Gisela, Vera, Manuel, Cabrera-Rode, Eduardo, Novoa, Lidia
• Format: Article
• Language: English
• Subjects: Adult; Alleles; ancestry; autoimmune; Case-Control Studies; Cuba; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Disease Susceptibility; Female; Gene Frequency; Genes, MHC Class II; Genetic Markers; Genetic Predisposition to Disease; genetics; Genotype; Haplotypes; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; human lymphocyte antigens; Humans; Male; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Assessment; Type 1 diabetes mellitus
• ISSN: 0301-4460; 1464-5033
• DOI: 10.3109/03014461003766984

Background: Incidence of type 1 diabetes varies widely around the world, probably due to ethnic differences across populations among other factors.Aims: To determine whether there is an association between disease and ancestry proportions; and to control disease-HLA associations for possible confounding by admixture or population stratification.Subjects and methods: 100 cases and 129 controls participated in the study. Ancestry informative markers, which have considerable differences in frequency between European, West African and Native American populations were used. Type 1 diabetes associated HLA susceptibility/protection alleles were ascertained by PCR using specific primers. Statistical analyses were conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 and STRAT 1.0 packages.Results: The results of logistic regression implemented in ADMIXMAP 3.7 indicated that European ancestry was associated with type 1 diabetes mellitus with an odds ratio of 5.7 corresponding to one unit change in European admixture proportion. Association was found between HLA alleles and disease, DQA1*0501, *0301 DQB1*0201 and DRB1*0301, *0401 being susceptibility alleles and DRB1*1501, DQA1*0102/3 and DQB1*0602 being protective alleles.Conclusions: We found an association between European ancestry and type 1 diabetes in our sample, indicating the contribution of ethnicity to incidence differences. Previously reported associations of HLA DR/DQ alleles with disease are confirmed for the admixed Cuban population.