Premium
Analysis of HLA Genotypes and Susceptibility to Insulin‐Dependent Diabetes Mellitus: HLA‐DQα Complements HLA‐DQβ
Author(s) -
BAISCH J. M.,
O'BRIEN M. E.,
HOOVER M. L.,
CAPRA J. D.
Publication year - 1992
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1992.tb03105.x
Subject(s) - hla dq , allele , genotype , human leukocyte antigen , diabetes mellitus , locus (genetics) , genetics , population , genetic predisposition , disease , immunology , medicine , biology , endocrinology , gene , antigen , haplotype , environmental health
It is well known that certain genes in the HLA‐D region confer increased susceptibility to insulin‐dependent diabetes mellitus (IDDM), Previous studies have documented an increased risk associated with the HLA‐DRβ chain alleles, DR3 and DR4, and the DQβ chain allele DQB1*0302 (formerly DQw8). Since DQα is also polymorphic and has been strongly implicated as the primary IDDM susceptibility locus in other races, we wanted to assess the contribution of DQα to IDDM in Caucasians, This information would enable us to define more precisely the class II association with IDDM as well as gain insight into issues of cu versus trans association of DQ heterodimers in this disease. To this end, the DQa genotype was determined for a large group of diabetic and normal Caucasian individuals who had been HLA‐DQβ and HLA‐DR typed previously. Using the polymerase chain reaction and a set of twelve oligonucleotide probes, we determined the DQα genotype of 323 patients with IDDM and 182 normal subjects. We found that certain DQα alleles are decreased in the diabetic population compared with normal subjects (i.e. DQA1*102 and 0103), while others are significantly increased in patients with IDDM (i.e. DQA 1*0301 and *0501), In addition, certain combinations of DQα alleles are associated with increased susceptibility to disease (i.e. DQA 1*0301, *0501), These results parallel our findings at the DQβ locus; however, because of the various associations between DQα and DQβ chains, the risks conferred by DQα are generally lower than those at DQβ, Moreover, our data indicate that, in Caucasians, no single DQα allele accounts for the highest degree of susceptibility to IDD M as in other races, although DQα analysis may be informative in a few cases. When done in combination, however, oligonucleotide analyses at both DQβ and DQα complement each other and provide a more complete assessment of the HLA‐associated component of disease susceptibility in IDDM