Academic Rheumatology Group, University of Sheffield, Sheffield, UK.
Rheumatology (Oxford). 2010 Jan;49(1):43-7. doi: 10.1093/rheumatology/kep372. Epub 2009 Nov 19.
To investigate the association between genotype at the soluble interleukin 6 receptor (sIL-6R) A358C single nucleotide polymorphism (SNP, rs8192284), previously reported to correlate with soluble receptor levels, and response to anti-TNF therapy in subjects with RA.
In a large cohort of Caucasian RA patients treated with anti-TNF medications (total, n = 1050; etanercept, n = 455; infliximab, n = 450; and adalimumab, n = 142), the sIL-6R A358C polymorphism was genotyped using a Taqman 5'-allelic discrimination assay. Linear regression analysis adjusted for baseline 28 joint disease activity score (DAS28), baseline HAQ score, gender and use of concurrent DMARDs was used to assess the association of genotype at this polymorphism with response to anti-TNF therapy, defined by change in DAS28 after 6 months of treatment. Analyses were performed in the entire cohort, and also stratified by an anti-TNF agent. Additional analysis according to the EULAR response criteria was also performed, with the chi-squared test used to compare genotype groups.
No association between genotype at sIL-6R A358C and response to anti-TNF treatment was detected either in the cohort as a whole or after stratification by anti-TNF agent, in either the linear regression analysis or with response segregated according to EULAR criteria.
This study shows that genotype at the functional sIL-6R A358C SNP is not associated with response to anti-TNF treatment in patients with RA.
探究可溶性白细胞介素 6 受体（sIL-6R）A358C 单核苷酸多态性（SNP，rs8192284）与抗 TNF 治疗反应的相关性，该 SNP 先前被报道与可溶性受体水平相关。
在一项接受抗 TNF 药物治疗的高加索人群 RA 患者的大型队列研究中（共 1050 例；依那西普 455 例、英夫利昔单抗 450 例、阿达木单抗 142 例），采用 Taqman 5'等位基因区分检测法对 sIL-6R A358C 多态性进行基因分型。采用线性回归分析，校正基线 28 关节疾病活动度评分（DAS28）、基线 HAQ 评分、性别和同时使用的 DMARDs，评估该多态性的基因型与抗 TNF 治疗反应的相关性，通过治疗 6 个月后 DAS28 的变化来定义。对整个队列进行分析，并按抗 TNF 药物进行分层分析。还根据 EULAR 反应标准进行了额外的分析，采用卡方检验比较基因型组。
在整个队列以及按抗 TNF 药物分层的分析中，无论是线性回归分析还是根据 EULAR 标准对反应进行分层，均未发现 sIL-6R A358C 处基因型与抗 TNF 治疗反应之间存在相关性。
本研究表明，RA 患者 sIL-6R A358C 功能性 SNP 基因型与抗 TNF 治疗反应无关。
