The polymorphic variable number of tandem repeats in the 5′ upstream region of the human insulin gene is a well-known non-human leukocyte antigen locus contributing to genetic susceptibility to IDDM. Controversy exists about the question as to whether INS susceptibility haplotypes are or are not preferentially inherited together with HLA-DR4 haplotypes. We investigated whether genetic interaction between INS and the HLA complex can be better defined using DQ genotypic and phenotypic markers in addition to DR serology. The 5′ INS 1/1 genotype was positively associated with IDDM both in non-DR4 subjects (relative risk = 4.3; 95% confidence interval, 1.6–11.5) and DR4 subjects (relative risk = 4.2; 95% confidence interval, 1.9–9.0). Further subdivision of IDDM patients and matched control subjects according to HLA-DQA1 and HLA-DQB1 genotype or phenotype also failed to show any association between 5′ INS and HLA class II genes in diabetic patients. The 5′ INS and HLA class II polymorphisms therefore provide independent risk markers, which may both contribute to the genetic screening of a high-risk population among nondiabetic individuals.
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Original Articles|
June 01 1993
5′ Insulin Gene Polymorphism Confers Risk to IDDM Independently of HLA Class II Susceptibility
Bart J Van Der Auwera;
Bart J Van Der Auwera
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Harry Heimberg;
Harry Heimberg
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Anneleen F Schrevens;
Anneleen F Schrevens
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Christine van Waeyenberge;
Christine van Waeyenberge
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Jocelyne Flament;
Jocelyne Flament
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Frans C Schuit
Frans C Schuit
Department of Biochemistry and Blood Transfusion Center, Vrije Universiteit Brussel
Brussels, Belgium
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Address correspondence and reprint requests to Dr. Frans C. Schuit, Department of Biochemistry, Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Diabetes 1993;42(6):851–854
Article history
Received:
January 11 1993
Revision Received:
January 28 1993
Accepted:
January 28 1993
PubMed:
8495808
Citation
Bart J Van Der Auwera, Harry Heimberg, Anneleen F Schrevens, Christine van Waeyenberge, Jocelyne Flament, Frans C Schuit; 5′ Insulin Gene Polymorphism Confers Risk to IDDM Independently of HLA Class II Susceptibility. Diabetes 1 June 1993; 42 (6): 851–854. https://doi.org/10.2337/diab.42.6.851
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