title: The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci.
abstract: The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of HLA-DRB1*04 haplotypes in 630 Sardinian newborns and 155 Sardinian IDDM patients. The different RRs and ARs of the various DR4-DQB1*0302 haplotypes, significantly ranging from the strongly associated DRB1*0405, DQB1*0302 to the protective DRB1*0403, DQB1*0302 haplotypes, provides clearcut evidence that the DRB1 locus is crucial in conferring IDDM predisposition or protection. Also, the DQB1 locus influences IDDM predisposition or protection by restricting the disease-positive association to DRB1*0405 haplotypes carrying the susceptibility DQB1*0302 or DQB1*0201 alleles but not the protective DQB1*0301 allele. Haplotype analysis not only suggests that the DRB1 and DQB1 loci influence IDDM risk in the same way, but also that the HLA-linked protection is "dominant" compared with "susceptibility." These results, obtained from a population with one of the highest IDDM incidences in the world, define more clearly the contribution of the various HLA loci to IDDM protection or susceptibility and allow a more precise calculation of AR.
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000276:immunology*; D006801:Humans; D007223:Infant; D007558:Italy
chemical_list: 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; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains