<i>HLA-DRB1</i> allele carrier frequencies in the SSc patients and the healthy controls.

<p><i>HLA-DRB1</i> allele carrier frequencies in the SSc patients and the healthy controls.</p

Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four Independent Protective Alleles, <i>DRB1*13</i>:<i>02</i>, <i>DRB1*14</i>:<i>06</i>, <i>DQB1*03</i>:<i>01</i>, and <i>DPB1*02</i>:<i>01</i>

<div><p>Objective</p><p>Several studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic sclerosis (SSc) have been reported. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are found in SSc patients. Here, we sought to identify <i>HLA</i> alleles associated with SSc in Japanese, and explored their associations with SSc phenotypes including the presence of autoantibodies.</p><p>Methods</p><p>Associations of <i>HLA-DRB1</i>, <i>DQB1</i>, <i>and DPB1</i> were analyzed in 463 Japanese SSc patients and 413 controls.</p><p>Results</p><p>We found that <i>DRB1*13</i>:<i>02</i> (<i>P</i> = 0.0011, <i>P</i>c = 0.0319, odds ratio [OR] 0.46, 95% confidence interval [CI] 0.29–0.73), <i>DRB1*14</i>:<i>06</i> (<i>P</i> = 6.60X10^-5, <i>Pc</i> = 0.0020, OR 0.05, 95%CI 0.01–0.41), <i>DQB1*03</i>:<i>01</i> (<i>P</i> = 0.0009, <i>Pc</i> = 0.0150, OR 0.56, 95%CI 0.40–0.79), and <i>DPB1*02</i>:<i>01</i> (<i>P</i> = 5.16X10^-6, <i>Pc</i> = 8.77X10^-5, OR 0.52, 95%CI 0.39–0.69) were protectively associated with SSc. In addition, these four alleles seemed to be independently associated with the protection against the susceptibility of SSc. On the other hand, we could not find predisposing alleles for overall SSc. With respect to SSc subsets, a tendency for these four alleles to be protectively associated was observed. However, there was a significant association between <i>DRB1*01</i>:<i>01</i>, <i>DRB1*10</i>:<i>01</i>, <i>DQB1*05</i>:<i>01</i>, and <i>DPB1*04</i>:<i>02</i> and the susceptibility to SSc with ACA. On the other hand, the presence of <i>DRB1*15</i>:<i>02</i>, <i>DQB1*06</i>:<i>01</i>, <i>DPB1*03</i>:<i>01</i>, and <i>DPB1*09</i>:<i>01</i> was associated with SSc with ATA.</p><p>Conclusion</p><p>Thus, the present study has identified protective associations of the four <i>HLA</i> class II alleles with overall Japanese SSc and predisposing associations of <i>HLA</i> class II alleles with Japanese SSc subsets.</p></div

Associations of amino acid residues in the DRβ (A, D, G), DQβ (B, E, H), or DPβ (C, F, I) chain with SSc (A, B, C), anti-centromere antibody- positive [ACA(+)] SSc (D, E, F), and anti-topoisomerase I antibody-positive [ATA(+)] SSc (G, H, I).

<p>Corrected <i>P</i> (<i>P</i>c) values were calculated by multiplying the <i>P</i> value by the number of amino acid residues tested. Associations were established by Fisher’s exact test using 2X2 contingency tables. Predisposing associations are indicated by filled circles and protective associations by open circles.</p

<i>HLA-DQB1</i> and <i>DPB1</i> allele carrier frequencies in the SSc patients and the healthy controls.

<p><i>HLA-DQB1</i> and <i>DPB1</i> allele carrier frequencies in the SSc patients and the healthy controls.</p