Five-year survival was not different between patients carrying the allele DRB1*15 in either group (overall p = 0.075; TxSLE p = 0.419; TxCTRL = 0.309).
Certain haplotype combinations, DRB1*07-DQβ1*03 (OR: 2.21; 95% CI:1.29-3.79, p<sub>c</sub> = 0.06, p = 0.00036) and DRβ1*07-DQβ1*05 (OR: 2.51, 95% CI: 1.34-4.71, p<sub>c</sub> = 0.07, p = 0.00039), had positive associations whereas DRβ1*14-DQβ1*03 (OR: 0.14, 95% CI: 0.061-0.36, p<sub>c</sub> = 2.34 × 10<sup>-5</sup>, p = 1.30 × 10<sup>-6</sup>) were found to have a significant negative association with SLE.
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.
Polymorphisms in several genes were associated with IL-6 levels (including IL10, TYK2, and CD40L in SLE and DRB1, NOD2, and CSF1 in RA) or with TNFα levels (including TNFSF4 and CSF2 in SLE and PTPN2, DRB1, and NOD2 in RA).
Significantly different carrier frequencies of certain DRB1 alleles were found to be associated with SLE as follows: increased DRB1*15:01 (P = 5.48×10⁻¹⁰, corrected P (Pc) = 1.59×10⁻⁸, odds ratio [OR] 2.17, 95% confidence interval [CI] 1.69-2.79), decreased DRB1*13:02 (P = 7.17×10⁻⁵, Pc = 0.0020, OR 0.46, 95% CI 0.34-0.63) and decreased DRB1*14:03 (P = 0.0010, Pc = 0.0272, OR 0.34, 95% CI 0.18-0.63).
In this study we have shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our lupus patients as well as in SLE patients with secondary APS.
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).
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).
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.
Overexpression of BAT1 mRNA was associated with carriers of a haplotype containing the LST1 marker transmitted to RA cases in a family study and also DRB1(*)15 associated with susceptibility to nephritis in systemic lupus erythematosus.
The associations found in the extended class I region could be markers for a 'novel' predisposing locus (loci) in SLE, adding to the risk conferred by DRB1*03 and B*08.
Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P < 0.0026].
The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations.
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 HLA profile distinguished the SLE-SS group from the SLE-no SS group, who had an increased frequency of DRB1*1501 and DQB1*0602 alleles, but was similar to the HLA profile of the primary SS group, who had an increased frequency of DRB1*0301.