Family-Based Association of HLA Class II Alleles and Haplotypes With Type I Diabetes in Brazilians Reveals Some Characteristics of a Highly Diversified Population Walkyria M. G. Volpini, Giuliana V. Testa, Sı ´lvia B. D. Marques, Lais I. Alves, Maria Elizabeth R. Silva, Se ´rgio A. Dib, Gil Guerra, Jr, Maria Fernanda V. M. Paulino, Sofia H. V. L. Marini, Lı ´gia B. L. Persoli, and Sophie Caillat-Zucman ABSTRACT: The association of HLA class II haplotypes with type I diabetes was analyzed in 56 Southeastern Brazilian families using affected family-based controls (AFBAC) method. DRB1-DQA1-DQB1 alleles were de- termined by polymerase chain reaction/sequence-specific primer genotyping. This study first revealed the great haplotype diversity of Brazilians (65 different haplotypes even with incomplete DRB1 subtyping), probably due to the admixture of Africans genes with European and Am- erindian genes in this population. The results revealed increased frequencies of the DRB1*03-DQA1*0501- DQB1*02 and DRB1*0401-DQA1*03-DQB1*0302 haplotypes in the patient group The highest risk for type I diabetes was associated with the heterozygote DRB1*03/*04 genotype as largely reported, and DRB1*03/X and DRB1*04/Y genotypes conferred a sig- nificant, but much lower disease risk. Protection from type I diabetes revealed some peculiarities in Southeastern Brazilians: a lack of significant protecting effect of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, and an apparent protection conferred by the DRB1*13- DQB1*0301, DRB1*11-DQB1*0301, and DRB1*01- DQB1*0501 two-locus haplotypes. The risk to type I diabetes in the highly diversified Southeastern Brazilians evidenced specific information to the prediction of the disease in this region of the country. Human Immunology 62, 1226 –1233 (2001). © American Society for Histo- compatibility and Immunogenetics, 2001. Published by Elsevier Science Inc. KEYWORDS: type I diabetes; HLA association; affected family-based control method; Brazilian population ABBREVIATIONS AFBAC affected family-based controls PCR polymerase chain reaction SSP sequence-specific primer HLA human leukocyte antigen HRR haplotype relative risk RR relative risk From the Laboratory of Histocompatibility (W.M.G.V., G.V.T., S.B.D.M., L.B.L.P.), Hemotherapy Center , and Department of Paediatrics (G.G., M.F.V.M.P., S.H.V.L.M.), Faculty of Medecine, University of Campinas, Campinas, Brazil; the Service of Endocrinology (L.I.A., M.E.R.S.), Faculty of Medecine, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil; the Service of Endocrinology (S.A.D.), Faculty of Medecine, Federal University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil; and the Laboratoire d’Immunologie (S.C.-Z.), Ho ˆpital Necker, Paris, France. Address reprint requests to: Dr. Walkyria M. G. Volpini, Laboratory of Histocompatibility, Hemotherapy Center, Rua Carlos Chagas, 480. Cidade Universita ´ria, Caixa postal 6198, 13081-970 Campinas-SP, Brazil; Tel: +55 (019) 3788-8728; Fax: +55 (019) 3788-8600; E-mail: walkyria@obelix.unicamp.br. Received May 29, 2001; revised July 4, 2001; accepted July 11, 2001. Human Immunology 62, 1226 –1233 (2001) 0198-8859/01/$–see front matter © American Society for Histocompatibility and Immunogenetics, 2001 Published by Elsevier Science Inc. S0198-8859(01)00323-8