Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, 1165 Copenhagen, Denmark.
Copenhagen Research Group for Inflammatory Skin, Herlev and Gentofte Hospital, 2730 Herlev, Denmark.
Int J Mol Sci. 2024 May 26;25(11):5793. doi: 10.3390/ijms25115793.
Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.
遗传生物标志物可能降低慢性炎症性疾病（如银屑病、银屑病关节炎、类风湿关节炎和炎症性肠病）治疗失败的风险。我们进行了一项系统评价和荟萃分析，评估了单核苷酸多态性（SNP）与生物制剂反应之间的关系。采用比值比（OR）和 95%置信区间（CI）进行荟萃分析。共纳入 185 项研究，涉及 62774 人。对于这些疾病，MYD88（rs7744）的次要等位基因与 TNFi 的良好反应相关（OR：1.24[1.02-1.51]，6 项研究，3158 例银屑病或类风湿关节炎患者），NLRP3（rs4612666）（OR：0.71[0.58-0.87]，5 项研究，3819 例类风湿关节炎或炎症性肠病患者）、TNF-308（rs1800629）（OR：0.71[0.55-0.92]，25 项研究，4341 例银屑病、类风湿关节炎或炎症性肠病患者）、FCGR3A（rs396991）（OR：0.77[0.65-0.93]，18 项研究，2562 例银屑病、银屑病关节炎、类风湿关节炎或炎症性肠病患者）和 TNF-238（rs361525）（OR：0.57[0.34-0.96]）与 TNFi 或英夫利昔单抗单独治疗的不良反应相关。TNFα、NLRP3、MYD88 和 FcRγ 基因的遗传变异与几种炎症性疾病对 TNFi 的反应有关。大多数与反应相关的其他遗传变异仅在少数研究中观察到，需要进一步验证。
