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

F Pérez-Bravo, J L Santos, E Carrasco, M Calvillán, C Albala, M Puig-Domingo, S Piquer, A De Leiva
Autoimmunity 2001, 33 (4): 285-91

AIM: The purpose of this study was to assess whether the transmission of DQB1*0201 and DQB1*0302 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 DQB1*0201 and DQB1*0302 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 DQB1*0201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1*201 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.

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