Department of Clinical Research, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, 204-8585, Japan.
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 252-0392, Japan.
Sci Rep. 2022 Jun 15;12(1):9916. doi: 10.1038/s41598-022-14116-x.
Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease characterized by the production of anti-U1 ribonucleoprotein antibodies and systemic symptoms similar to those of some other autoimmune diseases. HLA-DRB1 polymorphisms are important genetic risk factors for MCTD, but precise associations of DRB1 genotypes with MCTD have not been reported in Japanese people. Genotyping of HLA-DRB1 and -DQB1 was performed in Japanese MCTD patients (n = 116) and controls (n = 413). Associations of specific allele carriers and genotype frequencies with MCTD were analyzed.The following alleles were found to be associated with predisposition to MCTD: HLA-DRB104:01 (P = 8.66 × 10, Pc = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB109:01 (P = 0.0189, Pc = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB113:02 allele (P = 0.0032, Pc = 0.0929, OR 0.28, 95% CI 0.11‒0.72) was lower in MCTD patients than in controls. The frequencies of heterozygosity for HLA-DRB104:01/15 (P = 1.88 × 10, OR 81.54, 95% CI 4.74‒1402.63) and DRB109:01/15 (P = 0.0061, OR 2.94, 95% CI 1.38‒6.25) were also higher in MCTD patients. Haplotype and logistic regression analyses suggested a predisposing role for HLA-DRB104:01, DQB103:03, and a protective role for DRB113:02. Increased frequencies of HLA-DRB1*04:01/15 and DRB109:01/*15 heterozygous genotypes were found in Japanese MCTD patients.
混合性结缔组织病（MCTD）是一种罕见的系统性自身免疫性疾病，其特征是产生抗 U1 核糖核蛋白抗体和类似于某些其他自身免疫性疾病的全身症状。HLA-DRB1 多态性是 MCTD 的重要遗传危险因素，但在日本人中尚未报道 DRB1 基因型与 MCTD 的精确关联。对日本 MCTD 患者（n=116）和对照组（n=413）进行 HLA-DRB1 和-DQB1 基因分型。分析了特定等位基因携带者和基因型频率与 MCTD 的关联。发现以下等位基因与 MCTD 的易感性相关：HLA-DRB104:01（P=8.66×10，Pc=0.0003，比值比[OR]7.96，95%置信区间[CI]3.13-20.24）和 DRB109:01（P=0.0189，Pc=0.5468，OR 1.73，95%CI 1.12-2.67）。相比之下，MCTD 患者中 DRB113:02 等位基因的携带频率较低（P=0.0032，Pc=0.0929，OR 0.28，95%CI 0.11-0.72）。HLA-DRB104:01/15（P=1.88×10，OR 81.54，95%CI 4.74-1402.63）和 DRB109:01/15（P=0.0061，OR 2.94，95%CI 1.38-6.25）杂合性频率也较高。单体型和逻辑回归分析表明 HLA-DRB104:01、DQB103:03 具有易感性作用，DRB113:02 具有保护性作用。在日本 MCTD 患者中发现 HLA-DRB1*04:01/15 和 DRB109:01/*15 杂合基因型的频率增加。
