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.
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).
Finally, the low frequency of the DRB1*0301 and DRB1*1501 alleles in the control population suggests that the genetic admixture between Mexican Indians and Caucasian populations was an event that could have increased the risk of Mexicans to develop SLE.
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).
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.
HLA-DRB1*0301, DQA1*0501, DQB1*0201 was more common in Caucasians and DRB1*1503, DRB5*0101, DQA1*0102, DQB1*0602 in American blacks, regardless of age at SLE onset.
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.
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].
Our data suggested that the presence of C4AQ0 allele, DRB1*1501-DRB5*0101 haplotype and DR9 contributed to susceptibility to SLE in Koreans and that Korean SLE is based on a different genetic background from Caucasian patients.
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.
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).
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).
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).
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.
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.
The frequencies of the HLA class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2-associated haplotypes DRB1* 1501,DRB5*0101,DQB1*0602 and DRB1*1502,DRB5* 0102,DQB1*0501 were higher among SLE patients than among controls; however, only DQB1*0501 was statistically significantly associated with SLE.