DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis

被引:6
|
作者
Sanz-Garcia, Ancor [1 ]
Reolid, Alejandra [2 ]
Fisas, Laura H. [3 ]
Munoz-Aceituno, Ester [2 ]
Llamas-Velasco, Mar [2 ]
Sahuquillo-Torralba, Antonio [4 ]
Botella-Estrada, Rafael [5 ]
Garcia-Martinez, Jorge [1 ]
Navarro, Raquel [2 ]
Dauden, Esteban [2 ]
Abad-Santos, Francisco [3 ,6 ]
Ovejero-Benito, Maria C. [3 ,7 ]
机构
[1] La Princesa Univ Hosp, La Princesa Hlth Res Inst IIS IP, Data Anal Unit, Madrid, Spain
[2] La Princesa Univ Hosp, La Princesa Hlth Res Inst IIS IP, Dermatol Dept, Madrid, Spain
[3] Madrid Autonoma Univ UAM, La Princesa Hlth Res Inst IIS IP, La Princesa Univ Hosp, Teofilo Hernando Inst,Clin Pharmacol Dept, Diego de Leon 62, ES-28006 Madrid, Spain
[4] La Fe Univ & Polytech Hosp, Dermatol Dept, Valencia, Spain
[5] Univ Valencia, La Fe Univ & Polytech Hosp, La Fe Hlth Res Inst, Dermatol Dept, Valencia, Spain
[6] Carlos III Hlth Inst, Ctr Biomed Res Network Liver & Digest Dis CIBEReh, Madrid, Spain
[7] CEU San Pablo Univ, Sch Pharm, Madrid, Spain
关键词
pharmacogenomic; CNV; psoriasis; anti-TNF drug; methylation; METHYLATION; POLYMORPHISMS;
D O I
10.2340/00015555-3794
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study searched for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of anti-tumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methyl-ation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.
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页数:7
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