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以及其他 HLA-C 等位基因,以及 和 遗传变异与银屑病患者对抗 IL-17A 治疗的最佳反应相关。

and other HLA-C alleles, as well as and genetic variants associate with optimal response to anti-IL-17A treatment in patients with psoriasis.

机构信息

Laboratory of Experimental Immunology, IDI-IRCCS , Rome, Italy.

Section of Dermatology, Department of Medicine, University of Verona , Verona, Italy.

出版信息

Expert Opin Biol Ther. 2021 Feb;21(2):259-270. doi: 10.1080/14712598.2021.1862082. Epub 2020 Dec 28.

Abstract

: Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6 or HLA-Cw6 patient subpopulations, showing high or low responses to secukinumab, were also analyzed. : 417 SNPs were analyzed by Next-Generation Sequencing technology, in a cohort of 62 psoriatic patients and undergone secukinumab treatment. Univariate regression analysis was employed to examine the association between SNP and clinical response to secukinumab. Multivariate analysis was also performed to assess multivariate differences in SNP pattern of HLA-Cw6 or HLA-Cw6 patients showing high or low responses to secukinumab. : Eight SNPs in and upstream region (rs13207315, rs6900444, rs12189871, rs12191877, rs4406273, and rs10484554), including classical allele (rs1131118), and three in (rs9267325), (rs34085293) and (rs2304255) genes, associating with excellent response to secukinumab were identified. Importantly, rs34085293 or s2304255 SNP status defined a subgroup of super-responder patients. We also found that HLA-Cw6 and HLA-Cw6 patients carried out specific patterns of SNPs associating with different responses to secukinumab. : Assessment of , together with other allelic variants of genes, could be helpful to define patients which better benefit from anti-IL-17 therapy. PASI: Psoriasis Area and Severity Index; SNP: Single-Nucleotide Polymorphism Rs: Reference SNP; PASI75: 75% reduction in Psoriasis Area and Severity Index; PASI90: 90% reduction in Psoriasis Area and Severity Index; PASI100: 100% reduction in Psoriasis Area and Severity Index; NGS: Next-Generation Sequencing; OR: Odds Ratio; CAP: Canonical Analysis of Principal coordinates; BMI: Body Mass Index; LD: Linkage Disequilibrium.

摘要

我们的药物基因组学研究评估了银屑病风险基因座的遗传变异的存在/缺失对司库奇尤单抗临床反应的影响。还分析了单核苷酸多态性 (SNP) 模式特征,该模式特征将 HLA-Cw6 或 HLA-Cw6 患者亚群分为对司库奇尤单抗反应高或低的亚群。通过下一代测序技术分析了 62 名接受司库奇尤单抗治疗的银屑病患者的 417 个 SNP。采用单变量回归分析检查 SNP 与司库奇尤单抗临床反应之间的关联。还进行了多变量分析,以评估对司库奇尤单抗反应高或低的 HLA-Cw6 或 HLA-Cw6 患者 SNP 模式的多变量差异。在 基因及其上游区域(rs13207315、rs6900444、rs12189871、rs12191877、rs4406273 和 rs10484554)中发现了 8 个 SNP,包括经典等位基因(rs1131118),以及 3 个在 基因(rs9267325)、 基因(rs34085293)和 基因(rs2304255)中,与司库奇尤单抗的优异反应相关。重要的是,rs34085293 或 s2304255 SNP 状态定义了一个超级应答者患者亚组。我们还发现,HLA-Cw6 和 HLA-Cw6 患者携带特定的 SNP 模式,与对司库奇尤单抗的不同反应相关。评估 与基因的其他等位基因变异一起,可能有助于确定从抗 IL-17 治疗中获益更大的患者。PASI:银屑病面积和严重程度指数;SNP:单核苷酸多态性;rs:参考单核苷酸多态性;PASI75:银屑病面积和严重程度指数减少 75%;PASI90:银屑病面积和严重程度指数减少 90%;PASI100:银屑病面积和严重程度指数减少 100%;NGS:下一代测序;OR:优势比;CAP:主坐标的典范分析;BMI:体重指数;LD:连锁不平衡。

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