We analyzed 11 markers in the IDDM1 region in 120 IDDM patients and 83 healthy control subjects who were fully matched for the highest risk HLADQA1*O3O1-DQB1*O3O2/DQA1*O5O1-DQB1*O2O1 genotype. Our study provides strong evidence that two regions in the major histocompatibility complex contribute to IDDM susceptibility or protection. First, despite selection for highest IDDM-associated risk DQ genotypes, this region displays extensive linkage disequilibrium (LD) differences between IDDM patients and control subjects. A second critical region was mapped around the microsatellite locus D6S273 centromeric of TNF, and it is ∼200 kb in size. LD analysis shows that “diabetogenic haplotypes” may have resulted from a recombination telomeric of D6S1014 in the region of D6S273 and TNFa. Haplotype analysis using HLA and microsatellite loci refines IDDM risk assessment in carriers of the HLA-DQ highest risk genotype.
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Genetics|
February 01 1998
Genetic Structure of IDDM1: Two Separate Regions in the Major Histocompatibility Complex Contribute to Susceptibility or Protection
P Hanifi Moghaddam;
P Hanifi Moghaddam
Department of Immunohematology and Blood Bank, University Hospital
Leiden, The Netherlands
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P de Knijf;
P de Knijf
Department of Human Genetics, Leiden University
Leiden, The Netherlands
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B O Roep;
B O Roep
Department of Immunohematology and Blood Bank, University Hospital
Leiden, The Netherlands
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B Van der Auwera;
B Van der Auwera
Department of Biochemistry, Vrije Universiteit Brussel
Brussels, Belgium
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A Naipal;
A Naipal
Department of Immunohematology and Blood Bank, University Hospital
Leiden, The Netherlands
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F Gorus;
F Gorus
Department of Metabolism and Endocrinology, Vrije Universiteit Brussel
Brussels, Belgium
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F Schuit;
F Schuit
Department of Biochemistry, Vrije Universiteit Brussel
Brussels, Belgium
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M J Giphart;
M J Giphart
Department of Immunohematology and Blood Bank, University Hospital
Leiden, The Netherlands
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Address correspondence and reprint requests to Dr. M.J. Giphart, Department of Immunohematology and Blood Bank, Building 1, E3Q, University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Diabetes 1998;47(2):263–269
Article history
Received:
July 08 1997
Revision Received:
October 15 1997
Accepted:
October 15 1997
Citation
P Hanifi Moghaddam, P de Knijf, B O Roep, B Van der Auwera, A Naipal, F Gorus, F Schuit, M J Giphart, Belgian Diabetes Registry; Genetic Structure of IDDM1: Two Separate Regions in the Major Histocompatibility Complex Contribute to Susceptibility or Protection. Diabetes 1 February 1998; 47 (2): 263–269. https://doi.org/10.2337/diab.47.2.263
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