Complementation of HLA-DQA and -DQB genes confers susceptibility and protection to insulin-dependent diabetes mellitus.
Lack of an aspartic acid 57 in the HLA-DQ beta chain was introduced as a genetic marker of insulin-dependent diabetes mellitus (IDDM). Because 25% of the control population carries the same marker, we analyzed the DQ locus for the presence of more specific disease susceptibility markers, taking into account a possible role for the polymorphic DQA gene. We thereby identified the DQA3-DQB3.2/DQA4.1-DQB2 (DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201) genotype which was detected in 30% of the 268 typed IDDM patients and only in 1% of the 331 typed healthy controls, resulting in a relative risk of 35. This genetic marker was more frequent in patients with clinical onset before age 18 years (36%) than in patients diagnosed between age 18 and 40 years (22%) and was not observed in patients with non-IDDM. The new susceptibility genotype DQA3-DQB3.2/DQA4.1-DQB2 (DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201) may explain the well-known excess of DR3/DR4 heterozygous IDDM patients and is expected to help identify individuals at risk for developing the disease.
Heimberg
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H
Department of Biochemistry, Vrije Universiteit Brussel, Belgium.
Nagy
Z P
ZP
Somers
G
G
De Leeuw
I
I
Schuit
F C
FC
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001120:Arginine / Q000032:analysis; D001216:Asparagine / Q000032:analysis; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015342:DNA Probes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D005816:Genetic Complementation Test; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction
D015342:DNA Probes; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D001216:Asparagine; D001120:Arginine