Transmission 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 DQB10201 and DQB10302 alleles from heterozygous parents to Chilean type 1 diabetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected case.

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-parental design eliminates the possibility that case-controls differences are due to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and parents from n = 83 families using polymerase chain reaction and oligonucleotide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect immunofluorescence.

RESULTS

Transmission disequilibrium test indicate a strong association between DQB10201 and DQB10302 and type I diabetes. When comparing the two subsets of families defined by having an affected child tested negative or positive for GAD65 antibodies (39 and 44 case-parent trios respectively) the probability of transmission of DQB10201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1201 allele was also significantly different in the two subsets of families defined by ICA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No differences 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 associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.