Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study
Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid arthritis and response to anti-TNF drugs: a multicenter study
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DOI：
10.1097/fpc.0000000000000140
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发表时间：
2015-07-01
影响因子：
2.6
通讯作者：
Sainz, Juan
中科院分区：
文献类型：
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作者：
Canet, Luz M.;Filipescu, Ileana;Sainz, Juan
背景最近的研究表明，肿瘤坏死因子受体2（TNFRSF 1B）基因的遗传变异可能对类风湿性关节炎（RA）的易感性和药物反应产生影响。本人群为基础的病例对照研究进行了评估是否5标记TNFRSF 1B基因内的单核苷酸多态性（SNPs）与RA的风险和抗肿瘤坏死因子（TNF）drugs.MethodsThe研究人群包括1412 RA患者和1225名健康对照。一个子集的596抗TNF-初治RA患者被选中评估TNFRSF 1B单核苷酸多态性和药物反应的关联根据EULAR响应criteria.ResultsWe发现，运营商的TNFRSF 1B（rs3397 C）等位基因有显着增加的风险发展RA（P=0.0006）。重要的是，这种关联在多次测试校正后仍然显着。我们还证实了TNFRSF 1B（rs 1061622）SNP与RA风险之间的关联性，在单SNP分析中（P=0.89），但也通过有效的荟萃分析（P-DOM=0.67和P-REC=0.37，分别）。此外，我们的研究表明，TNFRSF 1B（rs3397 C/C），TNFRSF 1B（rs 1061622 G/G）和TNFRSF 1B（rs 1061631 A/A）基因型携带者对抗TNF药物反应较差的风险增加，P <0.05（P=0.014，0.0085和0.028，分别）。我们还观察到，根据对数加性模型，TNFRSF 1B（rs3397 C）或TNFRSF 1B（rs 1061622 G）等位基因携带者对抗TNF药物反应更差的风险增加（P=0.018和0.0059）。然而，TNFRSF 1B的关联（rs 1061622）根据对数相加模型，在多重检验校正后，SNP仅达到边缘显著性（P=0.0059），未通过荟萃分析证实结论TNFRSF 1B（rs3397）变异可能在调节RA发病风险中起作用，但是没有提供TNFRSF 1B变体在确定对抗TNF药物的应答中的影响的有力证据。
BackgroundRecent research suggests that genetic variants in the tumor necrosis factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to rheumatoid arthritis (RA) and drug response. The present population-based case-control study was carried out to evaluate whether 5 tagging single-nucleotide polymorphisms (SNPs) within the TNFRSF1B gene are associated with the risk of RA and response to antitumor necrosis factor (TNF) drugs.MethodsThe study population included 1412 RA patients and 1225 healthy controls. A subset of 596 anti-TNF-naive RA patients was selected to assess the association of TNFRSF1B SNPs and drug response according to the EULAR response criteria.ResultsWe found that carriers of the TNFRSF1B(rs3397C) allele had a significantly increased risk of developing RA (P=0.0006). Importantly, this association remained significant after correction for multiple testing. We also confirmed the lack of association of the TNFRSF1B(rs1061622) SNP with the risk of RA in the single-SNP analysis (P=0.89), but also through well-powered meta-analyses (P-DOM=0.67 and P-REC=0.37, respectively). In addition, our study showed that carriers of the TNFRSF1B(rs3397C/C), TNFRSF1B(rs1061622G/G), and TNFRSF1B(rs1061631A/A) genotypes had an increased risk of having a worse response to anti-TNF drugs at the level of P less than 0.05 (P=0.014, 0.0085 and 0.028, respectively). We also observed that, according to a log-additive model, carriers of the TNFRSF1B(rs3397C) or TNFRSF1B(rs1061622G) alleles showed an increased risk of having worse response to anti-TNF medications (P=0.018 and 0.0059). However, the association of the TNFRSF1B(rs1061622) SNP only reached marginal significance after correction for multiple testing according to a log-additive model (P=0.0059) and it was not confirmed through a meta-analysis (P-DOM=0.12).ConclusionOur results suggest that the TNFRSF1B(rs3397) variant may play a role in modulating the risk of RA, but does not provide strong evidence of an impact of TNFRSF1B variants in determining response to anti-TNF drugs.