We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLAclass II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRBl*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQAI*0501, "0102 and DQB1 "0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1 *03 and DQB1 "0201 alleles (p <10 -7, p corr. <10 -5 and p <10 -6, p corr. <10 -4, respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p <0.05, p corr. = n.s.). Analysis of linkage disequilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1 *02-positive patients and controls carry QAP1.2, and all DRB1 *03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1 *02 haplotypes, while the QAP4.1 variant can be observed in DRBI*03, *11, and "1303 haplotypes.
Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls.