Independent replication and meta analysis of association studies establish TNFSF4 as a susceptibility gene preferentially associated with the subset of anticentromere-positive patients with systemic sclerosis.
Independent replication and meta analysis of association studies establish TNFSF4 as a susceptibility gene preferentially associated with the subset of anticentromere-positive patients with systemic sclerosis.
复制标题
DOI：
10.3899/jrheum.111270
复制
发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Allanore Y
中科院分区：
文献类型：
--
作者：
Coustet B;Bouaziz M;Dieudé P;Guedj M;Bossini-Castillo L;Agarwal S;Radstake T;Martin J;Gourh P;Elhai M;Koumakis E;Avouac J;Ruiz B;Mayes M;Arnett F;Hachulla E;Diot E;Cracowski JL;Tiev K;Sibilia J;Mouthon L;Frances C;Amoura Z;Carpentier P;Cosnes A;Meyer O;Kahan A;Boileau C;Chiocchia G;Allanore Y
为了验证遗传易感性因素，需要进行大型队列的独立复制和遗传关联的荟萃分析。两项研究已发现已知的肿瘤坏死因子（配体）超家族成员 4 基因 (TNFSF4) 系统性红斑狼疮 (SLE) 风险位点与系统性硬化症 (SSc) 相关，但它们之间的基因型-表型相关性存在差异。我们的目标是验证 TNFSF4 与 SSc 的关联并确定风险较高的子集。对 1031 名 SSc 患者和 1014 名法国白人血统对照人群中已知的 SLE 和 SSc TNFSF4 易感性变异（rs2205960、rs1234317、rs12039904、rs10912580 和 rs844648）进行了基因分型。对现有数据进行了基因型-表型关联分析和荟萃分析，提供了 4,989 名 SSc 患者和 4,661 名对照者的群体研究，这些患者均为欧洲白人血统。观察到 5 个单核苷酸多态性 (SNP) 与抗着丝粒抗体 (ACA) 阳性的 SSc 患者子集存在等位基因和基因型关联，并且仅存在与 SSc 和有限皮肤 SSc 关联的趋势。 Rs2205960 在患有 SSc 的 ACA+ 患者中表现出最强的等位基因关联 [p = 0.0015； OR 1.37 (1.12–1.66)]，与 ACA 阳性 SSc 患者相比，具有显着的队列内相关性。荟萃分析证实了与 SSc 的总体关联，但也提高了与 ACA+ 子集的优先关联性，并且与 rs2205960 [T 等位基因 p = 0.00013；T 等位基因 p = 0.00013； OR 1.33 (1.15–1.54) 和 TT 基因型 p = 0.00046；或 2.02 (1.36–2.98)]。我们确认 TNFSF4 是 SSc 易感基因，rs2205960 是推定的因果变异，与 ACA+ SSc 亚表型优先相关。 （首次发布，2012 年 3 月 15 日；J Rheumatol 2012；39:997–1003；doi:10.3899/jrheum.111270）
Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk. Known SLE and SSc TNFSF4 susceptibility variants (rs2205960, rs1234317, rs12039904, rs10912580, and rs844648) were genotyped in 1031 patients with SSc and 1014 controls of French white ancestry. Genotype-phenotype association analysis and metaanalysis of available data were performed, providing a population study of 4989 patients with SSc and 4661 controls, all of European white ancestry. Allelic and genotypic associations were observed for the 5 single-nucleotide polymorphisms (SNP) with the subset of patients with SSc who are positive for anticentromere antibodies (ACA) and only a trend for association with SSc and limited cutaneous SSc. Rs2205960 exhibited the strongest allelic association in ACA+ patients with SSc [p = 0.0015; OR 1.37 (1.12–1.66)], with significant intracohort association when compared to patients with SSc positive for ACA. Metaanalysis confirmed overall association with SSc but also raised preferential association with the ACA+ subset and strongest effect with rs2205960 [T allele p = 0.00013; OR 1.33 (1.15–1.54) and TT genotype p = 0.00046; OR 2.02 (1.36–2.98)]. We confirm TNFSF4 as an SSc susceptibility gene and rs2205960 as a putative causal variant with preferential association in the ACA+ SSc subphenotype. (First Release March 15 2012; J Rheumatol 2012;39:997–1003; doi:10.3899/jrheum.111270)
登录
查看更多内容
影响因子：
5
作者：
Nordmark, G.;Kristjansdottir, G.;Syvanen, A-C
通讯作者：
Syvanen, A-C
影响因子：
3.9
作者：
Komura, Kazuhiro;Yoshizaki, Ayumi;Sato, Shinichi
通讯作者：
Sato, Shinichi
影响因子：
27.4
作者：
Diaz-Gallo LM;Gourh P;Broen J;Simeon C;Fonollosa V;Ortego-Centeno N;Agarwal S;Vonk MC;Coenen M;Riemekasten G;Hunzelmann N;Hesselstrand R;Tan FK;Reveille JD;Assassi S;García-Hernandez FJ;Carreira P;Camps MT;Fernandez-Nebro A;de la Peña PG;Nearney T;Hilda D;González-Gay MA;Airo P;Beretta L;Scorza R;Herrick A;Worthington J;Pros A;Gómez-Gracia I;Trapiella L;Espinosa G;Castellvi I;Witte T;de Keyser F;Vanthuyne M;Mayes MD;Radstake TR;Arnett FC;Martin J;Rueda B
通讯作者：
Rueda B
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.
影响因子：
30.8
作者：
Graham, Deborah S. Cunninghame;Graham, Robert R.;Manku, Harinder;Wong, Andrew K.;Whittaker, John C.;Gaffney, Patrick M.;Moser, Kathy L.;Rioux, John D.;Altshuler, David;Behrens, Timothy W.;Vyse, Timothy J.
通讯作者：
Vyse, Timothy J.