2 research outputs found
Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes
Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic
association with type 1 diabetes (T1DM) risk. OBJECTIVE: The objective of the
study was to analyze whether HLA DQ alleles influence the development of
antiislet autoantibodies, the progression to T1DM among autoantibody-positive
relatives, or both. DESIGN: The Diabetes Prevention Trial-1 screened more than
90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody
(ICA) expression between 1994 and 2002. SETTING: The study was conducted in the
general community. PARTICIPANTS: The Diabetes Prevention Trial-1 found 2817
ICA-positive relatives who were tested for biochemical autoantibodies (GAD65,
ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for
progression to diabetes for up to 8 yr (median, 3.6 yr). MAIN OUTCOME MEASURE:
Progression to T1DM was measured. RESULTS: High-risk DQ haplotypes and genotypes
were associated with a higher percentage of relatives expressing multiple
biochemical autoantibodies and higher T1DM risk (e.g., respectively, 59 and 36%
at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype).
The number of autoantibodies expressed significantly increased T1DM risk and
across different DQ genotypes, autoantibody positivity directly correlated with
diabetes risk. However, multivariate analyses indicated that the influence of
most genotypes on T1DM risk was not independent from autoantibody expression,
with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic
combinations conferred 5-yr diabetes risks significantly lower (e.g.
7%-DQA1*0201-DQB1*0201/DQA1*0501-DQB1*0201 and
14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201) than when those haplotypes were
found in other combinations. CONCLUSION: HLA DQ alleles determine autoantibody
expression, which is correlated with diabetes progression. Among
autoantibody-positive relatives, most HLA DQ genotypes did not further influence
T1DM risk