Abstract
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 diferences were in the DQA1∗0301 (RR = 3.62, p < 0.000005) and DQA1∗0501 (RR = 2.13, p < 0.05) alleles. DQB1∗0201 (RR = 4.1, p < 0.00005) and DQB1∗0302 (RR = 5.42, p < 0.000005) alleles were also significantly increased. A significant 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-DQA1∗0102-DQB1∗0602 and DRB1∗1401-DQA1 ∗0104-DQB1∗05031 protective haplotypes (RR = 0.17 and 0.09, p < 0.0005 and 0.05, respectively) were significantly lower in patients. The absence of Asp57 and the presence of Arg52 were associated with disease in a dose-dependent manner. Several genotypes encoding the identical DQα52/DQβ57 phenotype carried very different RRs. Finally, the Cantabrian population has the highest incidence of IDDM reported for Spain (15.2 of 100.000 in the 0–14 age group, Poisson’s 95% CI: 10.6–19.3).
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