Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis.
Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis.
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DOI：
10.1007/s00296-015-3235-z
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发表时间：
2015-08
影响因子：
4
通讯作者：
Feelders, R. A.
中科院分区：
文献类型：
--
作者：
Quax, R. A. M.;Koper, J. W.;Huisman, A. M.;Weel, A.;Hazes, J. M. W.;Lamberts, S. W. J.;Feelders, R. A.
关键词：
糖皮质激素(GC)广泛应用于类风湿性关节炎(RA)。由于GC耐药导致的持续活动性疾病可能会对RA的长期疾病结局产生不利影响。我们研究了糖皮质激素受体(GR)和糖皮质激素诱导转录本1(GLCCI1)基因多态性与类风湿关节炎患者糖皮质激素敏感性、疾病活动评分(DAS)和糖皮质激素桥接治疗疗效之间的关系。我们前瞻性地研究了138名新近发病或长期存在的类风湿关节炎患者的体内GC敏感性。在体内，GC敏感性表示为标准化GC治疗2周后DAS的相对减少。对所有患者进行GR基因BclI(Rs41423247)、N363S(Rs6195)、9β(Rs6198)、ER22/23EK(rs6189+rs6190)和GLCCI1变异体rs37972的基因分型，并将其分为携带与GC敏感性增加相关的多态(BclI-G等位基因、N363S-G等位基因、GLCCI1-C等位基因)或GC敏感性降低(9个β-G等位基因、ER22/23EK-A/A等位基因、GLCCI1-T等位基因)。用协方差分析和线性回归分析不同基因型组间基线DAS的差异和DAS的相对下降。携带GR和GLCCI1基因多态性与GC敏感性降低相关的患者的基线DAS较高。GLCCI1基因型与男性类风湿关节炎患者DAS的改善相关，而与GR基因型无关。GLCCI1基因微小等位基因(Rs37972)可能与男性RA患者GC桥联治疗效果不佳有关。BclI-G、N363S-G或GLCCI1-C等位基因携带者的基线疾病活动度较低，提示GLCCI1和GR基因在调节GC对内源性皮质醇的敏感性中发挥作用。
Glucocorticoids (GC) are widely used in rheumatoid arthritis (RA). Ongoing active disease due to GC resistance may unfavorably influence long-term disease outcome in RA. We studied the association between the presence of glucocorticoid receptor (GR) and glucocorticoid-induced transcript 1 (GLCCI1) gene polymorphisms, which modulate GC sensitivity, and baseline disease activity score (DAS) and efficacy of GC bridging therapy in RA. We prospectively studied in vivo GC sensitivity in 138 patients with recent-onset or longstanding RA. In vivo GC sensitivity was expressed as the relative decrease in DAS following 2 weeks of standardized GC therapy. All patients were genotyped for the GR polymorphisms BclI (rs41423247), N363S (rs6195), 9β (rs6198), ER22/23EK (rs6189 + rs6190), and the GLCCI1 variant rs37972 and subsequently divided in groups carrying a polymorphism associated with increased GC sensitivity (BclI-G allele, N363S-G allele, GLCCI1-C allele) or decreased GC sensitivity (9β-G allele, ER22/23EK-A/A allele, GLCCI1-T allele). Differences in baseline DAS and relative decrease in DAS in the different genotype groups were analyzed using analysis of covariance and linear regression. Baseline DAS was higher in patients who carried polymorphisms of the GR and GLCCI1 genes associated with decreased GC sensitivity. GLCCI1 genotype, but not GR genotypes, was associated with improvement in DAS in male patients with RA. The GLCCI1 gene minor allele (rs37972) may be associated with less efficient GC bridging therapy in male RA patients. Carriers of the BclI-G, N363S-G, or GLCCI1-C alleles had lower levels of baseline disease activity, suggesting a role for the GLCCI1 and GR gene in regulation of GC sensitivity to endogenously produced cortisol.
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影响因子：
2.8
作者：
Maltese, P.;Palma, L.;Magnani, M.
通讯作者：
Magnani, M.
DOI：
10.1056/nejmoa0911353
发表时间：
2011-09-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tantisira KG;Lasky-Su J;Harada M;Murphy A;Litonjua AA;Himes BE;Lange C;Lazarus R;Sylvia J;Klanderman B;Duan QL;Qiu W;Hirota T;Martinez FD;Mauger D;Sorkness C;Szefler S;Lazarus SC;Lemanske RF Jr;Peters SP;Lima JJ;Nakamura Y;Tamari M;Weiss ST
通讯作者：
Weiss ST
影响因子：
27.4
作者：
de Jong, Pascal Hendrik Pieter;Quax, Rogier A.;Hazes, J. M.
通讯作者：
Hazes, J. M.
DOI：
10.1111/j.1749-6632.2009.05013.x
发表时间：
2009-01-01
期刊：
GLUCOCORTICOIDS AND MOOD CLINICAL MANIFESTATIONS, RISK FACTORS, AND MOLECULAR MECHANISMS
影响因子：
--
作者：
Manenschijn, Laura;van den Akker, Erica L. T.;van Rossum, Elisabeth F. C.
通讯作者：
van Rossum, Elisabeth F. C.
影响因子：
4.9
作者：
Sokka T;Toloza S;Cutolo M;Kautiainen H;Makinen H;Gogus F;Skakic V;Badsha H;Peets T;Baranauskaite A;Géher P;Ujfalussy I;Skopouli FN;Mavrommati M;Alten R;Pohl C;Sibilia J;Stancati A;Salaffi F;Romanowski W;Zarowny-Wierzbinska D;Henrohn D;Bresnihan B;Minnock P;Knudsen LS;Jacobs JW;Calvo-Alen J;Lazovskis J;Pinheiro Gda R;Karateev D;Andersone D;Rexhepi S;Yazici Y;Pincus T;QUEST-RA Group
通讯作者：
QUEST-RA Group