The regulation of the expression of SH2D1A gene in systemic lupus erythematosus.

系统性红斑狼疮中SH2D1A基因表达的调控

• 批准号: 22591090
• 负责人: FURUKAWA Hiroshi
• 金额: $ 2.91万
• 依托单位: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591090/
• 关键词: 膠原病学; 疾患関連遺伝子; 全身性エリテマトーデス; SAP; 遺伝解析; SLE

SH2D1A, also known as SLAM-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (P=0.0110, odds ratio [OR] 1.97, 95% confidence interval [CI] 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (P=0.0067, OR 2.65, 95%CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele.

SH2D1A，也称为 SLAM 相关蛋白 (SAP)，是一种接头蛋白。最近，有报道称 SAP 缺陷小鼠可以免受系统性红斑狼疮 (SLE) 的侵害。在本研究中，我们假设SH2D1A基因是SLE的候选易感基因，并分析了其与SLE的关联。对 506 名日本女性 SLE 患者和 330 名健康女性对照者的 SH2D1A 区域的 5 个标签单核苷酸多态性 (SNP) 进行了病例对照关联研究。进行荧光素酶测定以确定 SNP 与 SLE 相关的功能作用。内含子 2 中的一个 SNP（rs2049995）显示与 SLE 相关（P=0.0110，比值比 [OR] 1.97，95% 置信区间 [CI] 1.16-3.34，在主导模型下）。 rs2049995 的关联似乎在发病年龄小于 20 岁的子集中更强（P=0.0067，OR 2.65，95%CI 1.28-5.46）。 rs2049995的功能评估表明，与抗性等位基因相比，易感等位基因的报告基因活性增加了1.9倍。

项目成果

Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope.

• DOI: 10.1371/journal.pone.0033133
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Furukawa H;Oka S;Shimada K;Sugii S;Ohashi J;Matsui T;Ikenaka T;Nakayama H;Hashimoto A;Takaoka H;Arinuma Y;Okazaki Y;Futami H;Komiya A;Fukui N;Nakamura T;Migita K;Suda A;Nagaoka S;Tsuchiya N;Tohma S
• 通讯作者: Tohma S

A novel HLA-DQB1*04 allele, DQB1*04:10, identified in a Japanese individual.

在日本个体中发现了一种新的 HLA-DQB1*04 等位基因 DQB1*04:10。

• 发表时间: 2013
• 期刊: Tissue Antigens
• 作者: Oka S;Furukawa H;Kashiwase K;Tsuchiya N;Tohma S.
• 通讯作者: Tohma S.

Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.

• DOI: 10.1371/journal.pone.0061044
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Génin E;Coustet B;Allanore Y;Ito I;Teruel M;Constantin A;Schaeverbeke T;Ruyssen-Witrand A;Tohma S;Cantagrel A;Vittecoq O;Barnetche T;Le Loët X;Fardellone P;Furukawa H;Meyer O;Fernández-Gutiérrez B;Balsa A;González-Gay MA;Chiocchia G;Tsuchiya N;Martin J;Dieudé P
• 通讯作者: Dieudé P

Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus

• DOI: 10.1177/0961203313479421
• 发表时间: 2013-04-01
• 期刊: LUPUS
• 影响因子: 2.6
• 作者: Furukawa, H.;Kawasaki, A.;Tohma, S.
• 通讯作者: Tohma, S.

Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients.

• DOI: 10.1371/journal.pone.0053910
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Furukawa H;Oka S;Shimada K;Sugii S;Hashimoto A;Komiya A;Fukui N;Nagai T;Hirohata S;Setoguchi K;Okamoto A;Chiba N;Suematsu E;Miyashita T;Migita K;Suda A;Nagaoka S;Tsuchiya N;Tohma S
• 通讯作者: Tohma S