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，也被称为slam相关蛋白（SAP），是一种适配蛋白。最近，有报道称SAP缺陷小鼠可免受系统性红斑狼疮（SLE）的侵袭。本研究假设SH2D1A基因为SLE的候选易感基因，并分析其与SLE的相关性。对506名日本女性SLE患者和330名健康女性进行了SH2D1A区域5标签单核苷酸多态性（snp）的病例对照研究。荧光素酶测定是为了确定与SLE相关的SNP的功能作用。内含子2中的一个SNP rs2049995显示与SLE相关（P=0.0110，优势比[OR] 1.97, 95%置信区间[CI] 1.16-3.34，优势模型下）。rs2049995的相关性似乎在发病年龄小于20岁的亚组中更强（P=0.0067, OR 2.65, 95%CI 1.28-5.46）。对rs2049995的功能评价表明，易感等位基因的报告基因活性比抗性等位基因提高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

Association of PHRF1-IRF7 region polymorphism with clinical manifestations of systemic lupus erythematosus in a Japanese population

• DOI: 10.1177/0961203312439333
• 发表时间: 2012-07-01
• 期刊: LUPUS
• 影响因子: 2.6
• 作者: Kawasaki, A.;Furukawa, H.;Tsuchiya, N.
• 通讯作者: Tsuchiya, N.

Genetic background of antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Japanese Population : association of STAT4 with myeloperoxidase antineutrophil cytoplasmic antibody-positive vasculitis

日本人群抗中性粒细胞胞浆抗体相关性血管炎的遗传背景：STAT4 与髓过氧化物酶抗中性粒细胞胞浆抗体阳性血管炎的关联

• 发表时间: 2012
• 作者: Kawasaki A;et al
• 通讯作者: et al

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.

Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study.

• DOI: 10.1186/ar3134
• 发表时间: 2010
• 期刊: Arthritis research & therapy
• 影响因子: 4.9
• 作者: Kawasaki A;Ito S;Furukawa H;Hayashi T;Goto D;Matsumoto I;Kusaoi M;Ohashi J;Graham RR;Matsuta K;Behrens TW;Tohma S;Takasaki Y;Hashimoto H;Sumida T;Tsuchiya N
• 通讯作者: Tsuchiya N