Genetic and immunological characteristics of Type I diabetes mellitus in an Indo-Aryan population

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 re latives (n = 146) and unrelated healthy control children (n = 54) were type d for alleles of the HLA-DRB1, HLA-DQA1 and HLA-DQB1 genes. Islet cell anti bodies and antibodies to glutamic acid decarboxylase, protein tyrosine phos phatase-2 (IA-2ic) and insulin were measured in the diabetic and control ch ildren. Results. The DRB1*03.DQA1*05.DQB1*02 haplotype was positively associated wi th the disease, occurring in 78% of diabetic children compared with 22.6 % of healthy children (p(c) < 2.4 x 10(-5)). In simplex families, this haplot ype was transmitted more frequently to the diabetic children than to their unaffected siblings (p < 1 x 10(-4)). The DRB1*04.DQA1* 03.DQB1*0302 haplot ype was also transmitted preferentially to the diabetic probands (p<0.025) but was not associated with disease in the case control study. Islet-relate d autoantibodies were detected in 89.6 % of diabetic patients compared with 11.8 % of control children (p <1 x 10(-6)). Although protein tyrosine phos phatase-2 autoantibodies were detected more frequently among DRB1*04-positi ve diabetic patients compared with patients lacking this allele, the overal l frequency of these autoantibodies was lower than observed in Europid diab etic 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 sim ilar to the disease observed in Angle-Europeans but has important immunogen etic differences. The low frequency of protein tyrosine phosphatase-2 autoa ntibodies among the Indo-Aryan diabetic children could have important impli cations for the design of future strategies for disease prediction in this population.