ISSN:
1432-0428
Schlagwort(e):
Keywords Type I diabetes, Indo-Aryan, immunogenetics, HLA genes, islet-related autoantibodies.
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
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]
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s001250051328
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