Title: Relative and absolute HLA-DQA1-DQB1 linked risk for developing type I diabetes before 40 years of age in the Belgian population: implications for future prevention studies
Authors: Van der Auwera, Bart J
Schuit, Frans
Weets, Ilse
Ivens, Ann
Van Autreve, Jan E
Gorus, Frans K # ×
Issue Date: Jan-2002
Publisher: Elsevier/North-Holland
Series Title: Human Immunology vol:63 issue:1 pages:40-50
Abstract: HLA-DQ genotyping remains the cornerstone of genetic risk stratification in type I diabetes prediction and prevention studies. We developed a genetic screening strategy for predisposition to type I diabetes in the Belgian population based upon HLA-DQA1-DQB1 typing and taking into account the age at clinical onset. A group of 1866 autoantibody-positive type I patients below age 40 years recruited by the Belgian Diabetes Registry and a group of 750 control subjects were DQA1-DQB1 genotyped. In the total study population 16 different DQA1-DQB1 haplotypes were revealed, allowing the stratification of 81 genotypes in ten different genotype groups. Apart from the highest risk DQA1*-DQB1* genotype 0301-0302/0501-0201 (odds ratio 21; absolute risk 6%), three other genotype groups conferred a highly significant disease risk (p < 10(-6)). Altogether, these susceptibility genotypes were carried by 9% of the control subjects versus 60% of the patients diagnosed before age 40 years and up to 70% of those under age 5 years. All other genotypes were protective, neutral, infrequent or associated with a moderate protection or susceptibility. A strong, although not absolute protection was conferred by DQB1*0602-positive haplotypes (odds ratio = 0.03). This study in a large cohort of autoantibody-positive patients shows that a DQA1-DQB1-based genotyping strategy allows the identification of a subgroup representing less than 10% of the Belgian population but harbouring the majority of future type I patients arising in childhood or early adulthood. Future prediction and prevention studies should take into account the age dependency of this HLA-DQ associated risk.
ISSN: 0198-8859
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
× corresponding author
# (joint) last author

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