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Analysis of HLA Genotypes and Susceptibility to Insulin‐Dependent Diabetes Mellitus: Association Maps Telomeric to HLA‐DP
Author(s) -
BAISCH J. M.,
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.tb03106.x
Subject(s) - allele , human leukocyte antigen , genotype , immunology , genetics , genetic predisposition , diabetes mellitus , population , polymerase chain reaction , locus (genetics) , biology , medicine , antigen , gene , endocrinology , environmental health
There is convincing evidence that certain combinations of alleles within the human leucocyte antigen (HLA) complex, particularly within HLA‐DQ, are associated with either resistance or susceptibility to insulin‐dependent diabetes mellitus (IDDM). A previous study conducted on a large, well‐defined grou p of patients demonstrated that DQB 1*0302 (DQw8) conferred ‘dominant susceptibility’ to IDDM while DQB 1*0602 (DQwl.2) conferred ‘dominant protection’. The availability of this population enabled us to further assess susceptibility associated with other class II alleles in an effort to map an outside HL A boundary of disease association. Using a group‐specific polymerase chain reaction protocol and a series of oligonucleotide probes which define over twenty DPβ alleles, we studied 286 unrelated Caucasian patients with IDDM and 184 normal subjects. We found that while several alleles are increased (DPB1*0201, DPB1*0301, DPB1*0402) or decreased (DPB1*0101, DPB1*0202) in the diabetic population compared with the normal subjects, the HL A association with IDDM is considerably weaker at the DP locus. These data define the centromeric boundary for the HLA‐associated susceptibility gene in IDDM, localizing susceptibility to the region telomeric to HLA‐DP up to and including HLA‐DQ