Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease.
Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease.
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DOI：
10.1038/s41598-022-14116-x
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发表时间：
2022-06-15
影响因子：
4.6
通讯作者：
Tohma, Shigeto
中科院分区：
文献类型：
--
作者：
Oka, Shomi;Higuchi, Takashi;Furukawa, Hiroshi;Shimada, Kota;Hashimoto, Atsushi;Komiya, Akiko;Matsui, Toshihiro;Fukui, Naoshi;Suematsu, Eiichi;Ohno, Shigeru;Kono, Hajime;Katayama, Masao;Nagaoka, Shouhei;Migita, Kiyoshi;Tohma, Shigeto
混合结缔组织病（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 核糖核蛋白抗体和与其他一些自身免疫性疾病相似的全身症状。 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。在日本 MCTD 患者 (n = 116) 和对照 (n = 413) 中进行了 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 易感性相关：HLA-DRB1*04:01 (P = 8.66 × 10–6, Pc = 0.0003, 比值比 [OR] 7.96, 95% 置信区间 [CI] 3.13-20.24) 和 DRB1*09:01 (P = 0.0189，Pc = 0.5468，OR 1.73，95% CI 1.12-2.67)。相反，MCTD 患者中 DRB1*13:02 等位基因的携带频率（P = 0.0032，Pc = 0.0929，OR 0.28，95% CI 0.11-0.72）低于对照组。 HLA-DRB1*04:01/*15 (P = 1.88 × 10–7, OR 81.54, 95% CI 4.74−1402.63) 和 DRB1*09:01/*15 (P = 0.0061, OR 2.94) 杂合性频率， MCTD 患者的 95% CI（1.38-6.25）也较高。单倍型和逻辑回归分析表明 HLA-DRB1*04:01、DQB1*03:03 具有诱发作用，DRB1*13:02 具有保护作用。日本 MCTD 患者中 HLA-DRB1*04:01/*15 和 DRB1*09:01/*15 杂合基因型的频率增加。
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-DRB1*04:01 (P = 8.66 × 10–6, Pc = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB1*09:01 (P = 0.0189, Pc = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB1*13:02 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-DRB1*04:01/*15 (P = 1.88 × 10–7, OR 81.54, 95% CI 4.74‒1402.63) and DRB1*09:01/*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-DRB1*04:01, DQB1*03:03, and a protective role for DRB1*13:02. Increased frequencies of HLA-DRB1*04:01/*15 and DRB1*09:01/*15 heterozygous genotypes were found in Japanese MCTD patients.
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影响因子：
3.7
作者：
Furukawa H;Kawasaki A;Oka S;Ito I;Shimada K;Sugii S;Hashimoto A;Komiya A;Fukui N;Kondo Y;Ito S;Hayashi T;Matsumoto I;Kusaoi M;Amano H;Nagai T;Hirohata S;Setoguchi K;Kono H;Okamoto A;Chiba N;Suematsu E;Katayama M;Migita K;Suda A;Ohno S;Hashimoto H;Takasaki Y;Sumida T;Nagaoka S;Tsuchiya N;Tohma S
通讯作者：
Tohma S
影响因子：
3.7
作者：
Oka S;Furukawa H;Yasunami M;Kawasaki A;Nakamura H;Nakamura M;Komori A;Abiru S;Nagaoka S;Hashimoto S;Naganuma A;Naeshiro N;Yoshizawa K;Yamashita H;Ario K;Ohta H;Sakai H;Yabuuchi I;Takahashi A;Abe K;Yatsuhashi H;Tohma S;Ohira H;Tsuchiya N;Migita K
通讯作者：
Migita K
影响因子：
2.3
作者：
Aringer, M;Steiner, G;Smolen, JS
通讯作者：
Smolen, JS
影响因子：
5.5
作者：
Flam, Siri Tennebo;Gunnarsson, Ragnar;Molberg, Oyvind
通讯作者：
Molberg, Oyvind
影响因子：
8
作者：
Paradowska-Gorycka, A.;Stypinska, B.;Jurkowska, M.
通讯作者：
Jurkowska, M.