title: HLA class II immunogenetics and incidence of insulin-dependent diabetes mellitus in the population of Cantabria (Northern Spain).
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. DQB*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-DQA *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 DQalpha52/DQbeta57 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).
authors.affiliation: Servicio de Immunología y Pediatría, Hospital Universitario Marques de Valdecilla, Instituto Nacional de la Salud, Santander, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Escribano-de-Diego
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Velasco
authors.forename: C
authors.initials: C
authors.lastname: Luzuriaga
authors.forename: J G
authors.initials: JG
authors.lastname: Ocejo-Vinyals
authors.forename: J E
authors.initials: JE
authors.lastname: Paz-Miguel
authors.forename: F
authors.initials: F
authors.lastname: Leyva-Cobián
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C553505:HLA-DRB1*04:01 antigen; C553506:HLA-DRB1*04:02 antigen; D000949:Histocompatibility Antigens Class II