DQCAR microsatellite polymorphisms in three selected HLA class II‐associated diseases

DQCAR is a very polymorphic CA repeat microsatellite located between the HLA DQAl and DQBl gene. Previous studies have shown that specific DQCAR alleles are in tight linkage disequilibrium with known HLA DR-DQ haplotypes. Of special interest was the fact that haplotypes containing long CA repeat alleles (DQCAR>lll> were gener- ally more polymorphic within and across ethnic groups. In these latter cases, several DQCAR alleles were found even in haplotypes containing the same flanking DQAl and DQBl alleles. In this work, three HLA class I1 associated diseases were studied using the DQCAR microsatellite. The aim of this study was to test if DQCAR typing could distinguish haplotypes with the same DRB1, DQAl and DQBl alleles in control and affected individuals. To do so, patients with selected HLA DR-DQ suscep- tibility haplotypes were compared with HLA DR and DQ matched con- trols. This included: Norwegian subjects with Celiac disease and the HLA DRB 1 *030 1, DQA 1 *050 1 1, DQB 1 *02 haplotype; Japanese subjects with Type 1 (insulin-dependent) Diabetes Mellitus and the HLA DRB1*0405, DQA1*0302, DQB1*0401 haplotype; and French patients with corticosensitive Idiopathic Nephrotic Syndrome and the HLA DRB 1 *070 1, DQA 1 *0201, DQB 1 *0202 haplotype. These specific haplo- types 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,DQ4-DQCAR 1 13 or 115 Idiopathic Nephrotic syndrome and DR7,DQ2-DQCAR 11 1-121). Additional DQCAR diversity was found in both control and patients bearing haplotypes with long CA repeat al- leles. The results indicate that DQCAR typing did not improve speci- ficity in combination with high resolution DNA HLA typing as a marker for these three disorders.