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在英国类风湿性关节炎队列中,补体受体1基因变异与开始抗TNF治疗患者的基线红细胞沉降率水平的关联:类风湿性关节炎遗传学和基因组学研究联盟队列生物制剂研究结果

Association of a complement receptor 1 gene variant with baseline erythrocyte sedimentation rate levels in patients starting anti-TNF therapy in a UK rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort.

作者信息

Bluett J, Ibrahim I, Plant D, Hyrich K L, Morgan A W, Wilson A G, Isaacs J D, Barton A

机构信息

Arthritis Research UK Epidemiology Unit, Manchester Academy of Health Science, University of Manchester, Manchester, UK.

NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

出版信息

Pharmacogenomics J. 2014 Apr;14(2):171-5. doi: 10.1038/tpj.2013.26. Epub 2013 Jul 16.

Abstract

Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129 (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR, baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion, genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28-ESR, indicating no adjustment for CR1 genotype is required in the assessment of patients with severe active RA.

摘要

在大多数欧洲国家,抗肿瘤坏死因子(TNF)疗法的适用对象仅限于重度活动性类风湿关节炎(RA)患者。DAS28评分是疾病严重程度的一个指标,纳入了两种炎症标志物之一,即红细胞沉降率(ESR)或C反应蛋白。我们旨在确定已知影响ESR的基因变异与活动性RA患者ESR水平之间的关系。对DNA样本进行基因分型,检测四个单核苷酸多态性(SNP),即rs7527798(CR1L)、rs6691117(CR1)、rs10903129(TMEM57)和rs1043879(C1orf63)。评估了SNP与基线ESR、基线DAS28-ESR以及DAS28-ESR变化之间的关联。基线ESR与CR1 rs6691117基因型显著相关(P=0.01)。未发现基线DAS28-ESR或DAS28-ESR变化之间存在相关性。总之,编码CR1的基因中的遗传变异可能会改变ESR水平,但不会改变DAS28-ESR,这表明在评估重度活动性RA患者时无需对CR1基因型进行调整。

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