In addition, the frequency of DRB1*11:04 alleles was significantly increased in ATA<sup>+</sup> SSc patients compared with ATA<sup>-</sup> SSc patients.<b>Conclusion:</b> DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04 were associated with the risk of SSc.
Paternal transmission of DRB1 alleles encoding a +2 charge 3rd HVR was significantly reduced in SSc patients compared with maternal transmission (p = 0.0003, corrected for analysis of four charge categories p = 0.001).
Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile-onset SSc versus 1.5% of controls; OR 7.48, P = 0.0002).
In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations.
Among the HLA-DR*15 alleles, the AF of the DRB1*15:02 was increased significantly in all SSc patients (29.0 vs 12.6%, Pc = 0.0219) and SSc patients with anti-Scl70+ (32.4 vs 12.6%, Pc = 0.0196).
To determine human leucocyte antigen-class II (HLA-class II) (DRB1, DQB1, DQA1 and DPB1) alleles, haplotypes and shared epitopes associated with scleroderma (systemic sclerosis (SSc)) and its subphenotypes in a large multi-ethnic US cohort by a case-control association study.
His HLA type included both the B27 allele conferring susceptibility to ankylosing spondylitis and the B35, DRB1 11, and DQB1 03 described as associated with systemic sclerosis.
The DRB1*11 allele was also observed more frequently in anti-topo I-positive SSc than in controls (13.3% vs. 4.2%) but not statistically significant (p = 0.053, p(corr) = 0.689).
Increased frequencies of DR2 in the overall SSc group (OR = 2.4), DRB1*0301 in the limited cutaneous SSc (lcSSc) subset (OR = 9.0), and DQB1*0301/4 in the diffuse cutaneous SSc (dcSSc) subset (OR = 9.0) were observed.
Among anti-topo I negative patients, diffuse and limited subtypes of SSc were significantly associated with DRB1*0803 (47% vs 15% in controls; Pcorr < 0.05) and DRB1*1501 (50% vs 17% in controls; Pcorr < 0.01), respectively.
Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese.
Association analysis among DMA, DMB, and DRB1*1502 in Japanese SSc with diffuse scleroderma and SSc with a-Scl-70 indicated that the increase in DMA*0101 was not primary, but reflected an increase in HLA DRB1*1502.
These data support the role of DR5 (DRB1*1104) in the genetic susceptibility to develop scleroderma in Mexican patients and also sustain the notion of genetically determined clinical subgroups of SSc.
Furthermore, the sharing of the particular amino acid sequence: valine38 and phenylalanine67-lysine68-glutamic acid69-asparic acid70-arginine71, by DRB5*0102, DRB1*0802 and DR11 (associated with Caucasian PSS) also suggests a contribution of the sequence in HLA-DR molecules to the pathogenesis of PSS according to the shared epitope hypothesis.