ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.
ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.
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DOI：
10.1371/journal.pone.0040067
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mimori T
中科院分区：
文献类型：
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作者：
Terao C;Ohmura K;Ikari K;Kochi Y;Maruya E;Katayama M;Yurugi K;Shimada K;Murasawa A;Honjo S;Takasugi K;Matsuo K;Tajima K;Suzuki A;Yamamoto K;Momohara S;Yamanaka H;Yamada R;Saji H;Matsuda F;Mimori T
人类白细胞抗原DRB1，特别是其共有表位(SE)与类风湿关节炎(RA)密切相关。然而，最近的研究表明，在没有抗瓜氨酸肽/蛋白抗体(ACPA)的情况下，SE与RA的相关性最弱。我们最近报道了ACPA阴性的类风湿关节炎与特定的HLA-DRB1等位基因和二倍型相关。在这里，我们试图通过根据类风湿因子(RF)阳性将ACPA阴性RA患者分为两组来检测ACPA阴性RA的遗传不同亚型。共收集了954例ACPA阴性RA患者和2个独立组的2,008名健康人的HL A-DRB1基因分型数据。比较ACPA阴性的RF阳性RA患者、ACPA阴性的RF阴性RA患者和对照组的HL A-DRB1等位基因和二倍型频率。并对综合结果进行了分析。对685例ACPA阳性的RA患者进行了类似的分析，根据他们的RF阳性进行分类。在联合分析中，HLADRB1*04：05和*09：01与ACPA阴性的RF阳性RA有很强的相关性(p = 分别为8.8万−6和0.0011，OR分别为1.5 7(1.2 8~1.91)和1.3 7(1.13~1.6 5))。我们还发现HLADR14和HLADR8纯合子与ACPA阴性的RF阴性RA相关(P = 分别为0.00022和0.00013，OR分别为1.5 2(1.2 1~1.89)和3.0 8(1.6 8~5.6 4))。这些关联倾向在每一组中都被发现。相反，我们没有检测到ACPA阳性RA亚群之间的任何显著差异。总之，在日本，根据RF阳性，ACPA阴性的RA包括两个遗传上不同的亚群，这两个亚群与HLA-DRB1表现出不同的相关性。ACPA阴性、RF阳性RA与HLA-DRB1*04：05和*09：01密切相关。ACPA阴性的RF阴性RA与DR14和HLA-DR8纯合子相关。
HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10−6 and 0.0011, OR: 1.57 (1.28–1.91) and 1.37 (1.13–1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21–1.89) and 3.08 (1.68–5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote.
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影响因子：
--
作者：
Lee, HS;Lee, KW;Bae, SC
通讯作者：
Bae, SC
影响因子：
30.8
作者：
Gregersen, Peter K.;Amos, Chistopher I.;Lee, Annette T.;Lu, Yue;Remmers, Elaine F.;Kastner, Daniel L.;Seldin, Michael F.;Criswell, Lindsey A.;Plenge, Robert M.;Holers, V. Michael;Mikuls, Ted R.;Sokka, Tuulikki;Moreland, Larry W.;Bridges, S. Louis, Jr.;Xie, Gang;Begovich, Ann B.;Siminovitch, Katherine A.
通讯作者：
Siminovitch, Katherine A.
影响因子：
30.8
作者：
Kochi, Yuta;Okada, Yukinori;Yamamoto, Kazuhiko
通讯作者：
Yamamoto, Kazuhiko
影响因子：
27.4
作者：
Ho, P. Y. P. C.;Barton, A.;Bruce, I. N.
通讯作者：
Bruce, I. N.
影响因子：
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作者：
Huizinga, TWJ;Amos, CI;Criswell, LA
通讯作者：
Criswell, LA