Haplotypes bearing the DRB1*1501/DQB1*0602 (DR2) and DRB1*0301/DQB1*0201 (DR3) alleles were present in nearly two-thirds of SLE cases and were significantly associated with disease susceptibility in both family-based and case-control study designs.
We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers.
Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08).
This association was independent of the SLE-association signal of HLA-DRB1 on 6p21.3, as it was significant after adjustment for SLE-risk DRB1 alleles (P=0.0012).
To investigate a possible involvement of HLA-class II alleles in the genetic predisposition for the formation of anti-U1-nRNP antibody-in systemic lupus erythematosus (SLE), genomic DNA of 178 patients was typed for the DRB1, DQA1 and DQB1 alleles using a polymerase chain reaction (PCR) and non-radioactive-oligonucleotide typing.
This may suggest that HLA class II molecules themselves and/or an unknown susceptibility gene located near the DQA1 and DRB1 loci are involved in the pathogenesis of SLE.
Sequential removal of SLE-associated DRB1 haplotypes revealed independent effects due to variation within OR2H2 (extended class I, rs362521, p = 0.006), CREBL1 (class III, rs8283, p = 0.01), and DQB2 (class II, rs7769979, p = 0.003, and rs10947345, p = 0.0004).