HLA class II immunogenetics and incidence of insulin-dependent diabetes mellitus in the population of Cantabria (Northern Spain)

HLA class II genes were analyzed to study IDDM susceptibility in Cantabria (Northern Spain). Patients showed highly significant increases in DRB1*0301 (RR = 4.581, p < 0.00005), DRB1*0401 (RR = 2.6, p < 0.05), DRB1*0402 (RR = 8.78, p < 0.05) and DRB1*0405 (RR = 14.73,p < 0.005). Highly significant d ifferences were in the DQA1*0301 (RR = 3.62, p < 0.000005) and DQA1*0501 (R R = 2.13, p < 0.05) alleles. DQB1*0201 (RR = 4.1, p < 0.00005) and DQB1*030 2 (RR = 5.42, p < 0.000005) alleles were also significantly increased. A si gnificant increase in DRB1*0402-DQA1*0301-DQB1*0302 (RR = 16.18, p < 0.05), DRB1*0405-DQA1"0301-DQB1*0302 (RR = 16.12, p < 0.05), DRB1*0301-DQA1*0501 DQB1*0201 (RR = 4.58, p < 0.00005) and DRB1*0401-DQA1*0301-DQB1*0302 (RR = 4.36, p < 0.005) was apparent in the diabetic group, while the DRB1*1501- D QA1*0102-DQB1*0602 and DRB1*1401-DQA1 *0104-DQB1*05031 protective haplotype s (RR = 0.17 and 0.09, p < 0.0005 and 0.05, respectively) were significantl y lower in patients. The absence of Asp57 and the presence of Arg52 were as sociated with disease in a dose-dependent: manner. Several genotypes encodi ng the identical DQ alpha 52/DQ beta 57 phenotype carried very different RR s. Finally, the Cantabrian population has the highest incidence of IDDM rep orted for Spain (15.2 of 100.000 in the 0-14 age group, Poisson's 95% CI: 1 0.6-19.3). (C) American Society for Histocompatibility and Immunogenetics, 1999. Published by Elsevier Science Inc.