DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes

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DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes. / Sanjeevi, C. B.; Höök, P.; Landin-Olsson, M.; Kockum, I.; Dahlquist, G.; Lybrand, T. P.; Lernmark, Å.

I: Tissue Antigens, Vol. 47, Nr. 4, 01.01.1996, s. 275-283.

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Sanjeevi, C. B. ; Höök, P. ; Landin-Olsson, M. ; Kockum, I. ; Dahlquist, G. ; Lybrand, T. P. ; Lernmark, Å. / DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes. I: Tissue Antigens. 1996 ; Vol. 47, Nr. 4. s. 275-283.

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TY - JOUR

T1 - DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes

AU - Sanjeevi, C. B.

AU - Höök, P.

AU - Landin-Olsson, M.

AU - Kockum, I.

AU - Dahlquist, G.

AU - Lybrand, T. P.

AU - Lernmark, Å

PY - 1996/1/1

Y1 - 1996/1/1

N2 - The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB1(*)0401 (62% patients and 25% controls; OR 4.95, p < 0.01) and (*)0404 (16% patients and 10% controls; OR 1.67, p < 0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB1(*)0302-DQA1(*)0301 (DQ8) (56% patients and 14% controls; OR 7.69, p < 0.01; 15% patients and 10% controls; OR 1.55, p < 0.05, respectively). When DRB1(*)0401 was linked to DQB1(*)0301-DQA1(*)0301 (DQ7) (6% patients and 11% controls; OR 0.52, p < 0.05), this DR4 subtypes was negatively associated with IDDM. Third, tests of strongest association allowed the following ranking of alleles or haplotypes: DQB1(*)0302-DQA1(*)0301 (DQ8) > DQB1(*)0302 > DRB1(*)0401 > DRB1(*)0404 and the association of DRB1(*)0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA-DQ as a primary genetic risk factor for IDDM.

AB - The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB1(*)0401 (62% patients and 25% controls; OR 4.95, p < 0.01) and (*)0404 (16% patients and 10% controls; OR 1.67, p < 0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB1(*)0302-DQA1(*)0301 (DQ8) (56% patients and 14% controls; OR 7.69, p < 0.01; 15% patients and 10% controls; OR 1.55, p < 0.05, respectively). When DRB1(*)0401 was linked to DQB1(*)0301-DQA1(*)0301 (DQ7) (6% patients and 11% controls; OR 0.52, p < 0.05), this DR4 subtypes was negatively associated with IDDM. Third, tests of strongest association allowed the following ranking of alleles or haplotypes: DQB1(*)0302-DQA1(*)0301 (DQ8) > DQB1(*)0302 > DRB1(*)0401 > DRB1(*)0404 and the association of DRB1(*)0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA-DQ as a primary genetic risk factor for IDDM.

KW - Genetic susceptibility

KW - HLA-DQ

KW - HLA-DR

KW - IDDM

U2 - 10.1111/j.1399-0039.1996.tb02554.x

DO - 10.1111/j.1399-0039.1996.tb02554.x

M3 - Article

C2 - 8773316

AN - SCOPUS:0029968375

VL - 47

SP - 275

EP - 283

JO - Tissue Antigens

JF - Tissue Antigens

SN - 0001-2815

IS - 4

ER -