Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus

Jeanine M. Baisch, Tracy Weeks, Robert Giles, Marie Hoover, Peter Stastny, J. Donald Capra

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Abstract

There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles. Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P<0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ("dominant protection"). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/ DQw8 haplotype ("dominant susceptibility"). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8. We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.

Original languageEnglish (US)
Pages (from-to)1836-1841
Number of pages6
JournalNew England Journal of Medicine
Volume322
Issue number26
StatePublished - Jun 28 1990

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HLA-DQ Antigens
Type 1 Diabetes Mellitus
Genotype
Alleles
HLA-DQ beta-Chains
Haplotypes
Histocompatibility Testing
Oligonucleotide Probes
Histocompatibility Antigens Class II
Disease Susceptibility
HLA Antigens
Aspartic Acid
HLA-DQ8 antigen

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Baisch, J. M., Weeks, T., Giles, R., Hoover, M., Stastny, P., & Capra, J. D. (1990). Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. New England Journal of Medicine, 322(26), 1836-1841.

Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. / Baisch, Jeanine M.; Weeks, Tracy; Giles, Robert; Hoover, Marie; Stastny, Peter; Capra, J. Donald.

In: New England Journal of Medicine, Vol. 322, No. 26, 28.06.1990, p. 1836-1841.

Research output: Contribution to journalArticle

Baisch, JM, Weeks, T, Giles, R, Hoover, M, Stastny, P & Capra, JD 1990, 'Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus', New England Journal of Medicine, vol. 322, no. 26, pp. 1836-1841.
Baisch JM, Weeks T, Giles R, Hoover M, Stastny P, Capra JD. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. New England Journal of Medicine. 1990 Jun 28;322(26):1836-1841.
Baisch, Jeanine M. ; Weeks, Tracy ; Giles, Robert ; Hoover, Marie ; Stastny, Peter ; Capra, J. Donald. / Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. In: New England Journal of Medicine. 1990 ; Vol. 322, No. 26. pp. 1836-1841.
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abstract = "There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles. Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P<0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ({"}dominant protection{"}). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/ DQw8 haplotype ({"}dominant susceptibility{"}). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8. We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.",
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