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.
OBJECTIVE
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.


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.


CONCLUSIONS
Our results reveal that DQB1*0201 allele may display distinct associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.
Pérez-Bravo
F
F
Molecular Biology Laboratory, INTA, University of Chile, Santiago, Spain. fperez@uec.inta.uchile.cl
Santos
J L
JL
Carrasco
E
E
Calvillán
M
M
Albala
C
C
Puig-Domingo
M
M
Piquer
S
S
De Leiva
A
A
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002677:Chile; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D010290:Parents
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C051568:HLA-DQ1 antigen; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2