Cucca, Francesco and Lampis, Rosanna and Frau, Fulvia and Macis, Maria Doloretta and Angius, Efisio and Masile, Paolo and Chessa, Margherita and Frongia, Anna Paola and Silvetti, Mario and Cao, Antonio and De Virgiliis, Stefano and Congia, Mauro (1995) The Distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci. Human Immunology, Vol. 43 (4), p. 301-308. ISSN 0198-8859. Article.
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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 clear-cut 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.
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