Transmisson of high-risk HLA-DQB1 alleles in Chilean type 1 diabetic patients and their parents: Stratification by the presence of ICA or GAD65 autoantibodies

Aim The purpose of this study was to assess whether the transmission of DQB 1*0201 and DQB1*0302 alleles from heterozygous parents to Chilean type 1 di abetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected c ase. Material and Methods A study of incident type 1 diabetic cases and parents was carried out in Santiago, Chile during 1997-98. The use of the case-pare ntal design eliminates the possibility that case-controls differences are d ue to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and p arents from n = 83 families using polymerase chain reaction and oligonucleo tide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect im munofluorescence. Results Transmission disequilibrium test indicate a strong association betw een DQB1*0201 and DQB1*0302 and type 1 diabetes. When comparing the two sub sets of families defined by having an affected child tested negative or pos itive for GAD65 antibodies (39 and 44 case-parent trios respectively) the p robability of transmission of DQB1*0201 significantly differed between such strata (p-value = 0.025). The pattern of transmission of DQB1*201 allele w as also significantly different in the two subsets of families defined by I CA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No diffe rences were found in the transmission of DQB1*0302 allele in the different strata defined by the autoimmunity status of the proband. Conclusion Our results reveal that DQB1*0201 allele may display distinct as sociations with type 1 diabetes depending on the autoimmunity to ICA and GA D65 autoantibodies.