caa a22 4500 475772393 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s001250051328 doi (NATIONALLICENCE)springer-10.1007/s001250051328 Genetic and immunological characteristics of Type I diabetes mellitus in an Indo-Aryan population [Elektronische Daten] [M. A. Kelly, N. S. Alvi, N. J. Croft, C. H. Mijovic, G. F. Bottazzo, A. H. Barnett] Abstract : Aims/hypothesis. Our aim was to characterise the genetic and immunological features associated with Type I (insulin-dependent) diabetes mellitus in a cohort of Indo-Aryan children resident in the United Kingdom.¶Methods. Children with Type I diabetes (n = 53), unaffected first-degree relatives (n = 146) and unrelated healthy control children (n = 54) were typed for alleles of the HLA-DRB1, HLA-DQA1 and HLA-DQB1 genes. Islet cell antibodies and antibodies to glutamic acid decarboxylase, protein tyrosine phosphatase-2 (IA-2ic) and insulin were measured in the diabetic and control children.¶Results. The DRB1*03.DQA1*05.DQB1*02 haplotype was positively associated with the disease, occurring in 78 % of diabetic children compared with 22.6 % of healthy children (p c < 2.4 × 10-5). In simplex families, this haplotype was transmitted more frequently to the diabetic children than to their unaffected siblings (p < 1 × 10-4). The DRB1*04.DQA1* 03.DQB1*0302 haplotype was also transmitted preferentially to the diabetic probands (p < 0.025) but was not associated with disease in the case control study. Islet-related autoantibodies were detected in 89.6 % of diabetic patients compared with 11.8 % of control children (p < 1 × 10-6). Although protein tyrosine phosphatase-2 autoantibodies were detected more frequently among DRB1*04-positive diabetic patients compared with patients lacking this allele, the overall frequency of these autoantibodies was lower than observed in Europid diabetic subjects. This could reflect the absence of a disease association with DRB1*04 in the Indo-Aryan cohort.¶Conclusion/interpretation. Type I diabetes in our Indo-Aryan cohort is similar to the disease observed in Anglo-Europeans but has important immunogenetic differences. The low frequency of protein tyrosine phosphatase-2 autoantibodies among the Indo-Aryan diabetic children could have important implications for the design of future strategies for disease prediction in this population. [Diabetologia (2000) 43: 450-456] Springer-Verlag Berlin Heidelberg, 2000 Keywords Type I diabetes, Indo-Aryan, immunogenetics, HLA genes, islet-related autoantibodies nationallicence Kelly M. A. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut Alvi N. S. Birmingham Children's Hospital, Birmingham, UK, GB aut Croft N. J. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut Mijovic C. H. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut Bottazzo G. F. Scientific Directorate, Bambino Gesú Paediatric Hospital, Scientific Institute, Rome, Italy, IT aut Barnett A. H. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut https://doi.org/10.1007/s001250051328 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051328 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kelly M. A. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut NATIONALLICENCE 700 1- Alvi N. S. Birmingham Children's Hospital, Birmingham, UK, GB aut NATIONALLICENCE 700 1- Croft N. J. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut NATIONALLICENCE 700 1- Mijovic C. H. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut NATIONALLICENCE 700 1- Bottazzo G. F. Scientific Directorate, Bambino Gesú Paediatric Hospital, Scientific Institute, Rome, Italy, IT aut NATIONALLICENCE 700 1- Barnett A. H. Department of Medicine, Division of Medical Sciences, University of Birmingham, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer