Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region.
Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region.
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DOI：
10.1186/ar2516
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发表时间：
2008
影响因子：
4.9
通讯作者：
Tsuchiya N
中科院分区：
文献类型：
--
作者：
Kawasaki A;Ito I;Hikami K;Ohashi J;Hayashi T;Goto D;Matsumoto I;Ito S;Tsutsumi A;Koga M;Arinami T;Graham RR;Hom G;Takasaki Y;Hashimoto H;Behrens TW;Sumida T;Tsuchiya N
最近的研究发现STAT 4（信号转导和转录激活因子-4）是系统性红斑狼疮（SLE）的易感基因。STAT 1在2q32.2-q32.3上与STAT 4相邻编码，在SLE患者的外周血单核细胞中上调，并且在功能上与SLE相关。这项研究的目的是测试STAT 4是否与日本人群中的SLE相关，以确定风险单倍型，并检查STAT 1的潜在遗传贡献。为了实现这些目标，我们进行了全面的关联分析52标签单核苷酸多态性（SNP），包括STAT 1-STAT 4区域。在第一次筛选中，基于HapMap Phase II JPT（日本东京的日本人）数据选择52个标签SNP，并对105名患有SLE的日本女性患者和102名女性对照进行病例对照关联分析。对于相关的SNPs，对另外的病例和对照进行基因分型，并使用308例SLE患者和306例对照分析相关性。用Haploview 4.0版软件进行单倍型频率估计和使用排列检验的关联研究。估计人群归因危险度百分比，以比较人群中危险基因型的流行病学意义。在第一次筛查中，STAT 4中的rs7574865、rs 11889341和rs 10168266最显著相关（P < 0.01）。没有观察到STAT 1的显著相关性。随后对308名SLE患者和306名对照者进行的三个SNP的关联研究证实了rs7574865 T等位基因的强关联性（SLE组：46.3%，对照组：33.5%，P = 4.9 × 10-6，比值比1.71）以及TTT单倍型（rs 10168266/rs 11889341/rs7574865）（P = 1.5 × 10-6）。在SLE肾炎和抗双链DNA抗体亚组中，相关性更强。据估计，日本人群（40.2%）的人群归因风险百分比高于欧洲裔美国人（19.5%）。在白种人和日本人群中相同的STAT 4危险等位基因与SLE相关。没有证据表明STAT 1在SLE遗传易感性中起作用。STAT 4对SLE遗传背景的贡献在日本人群中可能大于欧洲血统的美国人。
Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 × 10-6, odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the Japanese population than in Americans of European descent.
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影响因子：
158.5
作者：
Remmers, Elaine F.;Plenge, Robert M.;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
4.4
作者：
Mathur, Anubhav N.;Chang, Hua-Chen;Kaplan, Mark H.
通讯作者：
Kaplan, Mark H.
STAT4遗传关联的特异性是针对全身性红斑狼疮的严重疾病表现。
影响因子：
4.5
作者：
Taylor, Kimberly E.;Remmers, Elaine F.;Lee, Annette T.;Ortmann, Ward A.;Plenge, Robert M.;Tian, Chao;Chung, Sharon A.;Nititham, Joanne;Hom, Geoffrey;Kao, Amy H.;Demirci, F. Yesim;Kamboh, M. Ilyas;Petri, Michelle;Manzi, Susan;Kastner, Daniel L.;Seldin, Michael F.;Gregersen, Peter K.;Behrens, Timothy W.;Criswell, Lindsey A.
通讯作者：
Criswell, Lindsey A.
影响因子：
4.4
作者：
Harigai, Masayoshi;Kawamoto, Manabu;Miyasaka, Nobuyuki
通讯作者：
Miyasaka, Nobuyuki
影响因子：
20.3
作者：
Durali, D;de Herve, MGD;Taoufik, Y
通讯作者：
Taoufik, Y