DQCAR MICROSATELLITE POLYMORPHISMS IN 3 SELECTED HLA CLASS II-ASSOCIATED DISEASES

DQCAR is a very polymorphic CA repeat microsatellite located between t he HLA DQA1 and DQB1 gene. Previous studies have shown that specific D QCAR alleles are in tight linkage disequilibrium with known HLA DR-DQ haplotypes. Of special interest was the fact that haplotypes containin g long CA repeat alleles (DQCAR>111) were generally more polymorphic w ithin and across ethnic groups. In these latter cases, several DQCAR a lleles were found even in haplotypes containing the same flanking DQA1 and DQB1 alleles. In this work, three HLA class II associated disease s were studied using the DQCAR microsatellite. The aim of this study w as to test if DQCAR typing could distinguish haplotypes with the same DRB1, DQA1 and DQB1 alleles in control and affected individuals. To do so, patients with selected HLA DR-DQ susceptibility haplotypes were c ompared with HLA DR and Do matched controls. This included: Norwegian subjects with Celiac disease and the HLA DRB10301, DQA1*05011, DQB1*0 2 haplotype; Japanese subjects with Type I (insulin-dependent) Diabete s Mellitus and the HLA DRB10405, DQA1*0302, DQB1*0401 haplotype; and French patients with corticosensitive Idiopathic Nephrotic Syndrome an d the HLA DRB10701, DQA1*0201, DQB1*0202 haplotype. These specific ha plotypes were selected from our earlier work to include one haplotype bearing a short DQCAR allele (celiac disease and DR3,DQ2-DQCAR99) and two haplotypes bearing long DQCAR alleles (Diabetes Mellitus and DR4,D Q4-DQCAR 113 or 115 Idiopathic Nephrotic syndrome and DR7,DQ2-DQCAR 11 1-121). Additional DQCAR diversity was found in both control and patie nts bearing haplotypes with long CA repeat alleles. The results indica te that DQCAR typing did not improve specificity in combination with h igh resolution DNA HLA typing as a marker for these three disorders.