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维生素D相关基因作为阿达木单抗治疗的克罗恩病患者临床缓解的预测生物标志物:一项初步研究

Vitamin D-Related Genetics as Predictive Biomarker of Clinical Remission in Adalimumab-Treated Patients Affected by Crohn's Disease: A Pilot Study.

作者信息

Cusato Jessica, Bertani Lorenzo, Antonucci Miriam, Tomasello Cristina, Caviglia Gian Paolo, Dibitetto Simone, Massano Alessandro, Mangia Michela, Mula Jacopo, Ceccarelli Linda, Costa Francesco, Zanzi Federico, Astegiano Marco, Ribaldone Davide Giuseppe, D'Avolio Antonio

机构信息

Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy.

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy.

出版信息

Pharmaceuticals (Basel). 2021 Nov 27;14(12):1230. doi: 10.3390/ph14121230.

Abstract

Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn's disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. ADA trough levels were associated with VD concentrations in patients with IBD, but no data are present in the literature concerning VD pathway-related gene single-nucleotide polymorphisms (SNPs) in affecting clinical outcomes. For this reason, the aim of this study was to evaluate the ability of VD-related genetics to predict clinical remission at 3 and 12 months in patients affected by CD treated with ADA. Patients affected by CD were included in this study. SNPs in , , , and genes were analyzed through real-time PCR. A total of 63 patients were enrolled. Calprotectin, hemoglobin, and C-reactive protein levels were influenced by SNPs in , , and genes. After 3 months of therapy, clinical remission was predicted by smoke, systemic steroids, and BsmI, whereas at 12 months by 1296AA/AC and VD supplementation. This study reports the association between VD pathway-related genetics and ADA treatment. Further studies are needed to confirm these promising data.

摘要

阿达木单抗(ADA)是一种人抗肿瘤坏死因子(TNF-α)单克隆抗体,用于治疗炎症性肠病,如克罗恩病(CD)。维生素D(VD)对于生物学功能很重要,例如调节参与药物代谢和转运的酶及转运蛋白编码基因的表达。IBD患者的ADA谷浓度与VD浓度相关,但文献中尚无关于VD通路相关基因单核苷酸多态性(SNP)对临床结局影响的数据。因此,本研究的目的是评估VD相关遗传学在预测接受ADA治疗的CD患者3个月和12个月时临床缓解的能力。本研究纳入了CD患者。通过实时PCR分析了、、和基因中的SNP。共招募了63例患者。钙卫蛋白、血红蛋白和C反应蛋白水平受、和基因中SNP的影响。治疗3个月后,吸烟、全身用类固醇和BsmI可预测临床缓解,而在12个月时,1296AA/AC和补充VD可预测临床缓解。本研究报道了VD通路相关遗传学与ADA治疗之间的关联。需要进一步研究来证实这些有前景的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb8/8706953/368bfef7e814/pharmaceuticals-14-01230-g001.jpg

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