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

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 less than 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.

• Authors: J M Baisch, T Weeks, R Giles, M Hoover, P Stastny, J D Capra
• Journal: The New England journal of medicine (N Engl J Med) Vol. 322 Issue 26 Pg. 1836-41 (Jun 28 1990) ISSN: 0028-4793 [Print] United States
• PMID: 2348836 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQ1 antigen
• HLA-DQ2 antigen
• HLA-DQ8 antigen
• HLA-DQbeta antigen

Topics

• Adult
• Alleles
• Base Sequence
• Diabetes Mellitus, Type 1 (genetics)
• Disease Susceptibility
• Female
• Genotype
• HLA-DQ Antigens (analysis)
• HLA-DQ beta-Chains
• Humans
• Male
• Molecular Sequence Data
• Nucleotide Mapping
• Polymerase Chain Reaction