Whole Exome Sequencing in Psoriasis Patients Contributes to Studies of Acitretin Treatment Difference

• Published in: International journal of molecular sciences 2017-02, Vol.18 (2), p.295-295
• Main Authors: Zhou, Xingchen, He, Yijing, Kuang, Yehong, Li, Jie, Zhang, Jianglin, Chen, Mingliang, Chen, Wangqing, Su, Juan, Zhao, Shuang, Liu, Panpan, Chen, Menglin, Shen, Minxue, Chen, Xiaoping, Zhu, Wu, Chen, Xiang
• Format: Article
• Language: English
• Subjects: acitretin; Acitretin - therapeutic use; Adult; Aged; Alleles; Exome; Female; Genetic diversity; Genetic markers; genetic variation; High-Throughput Nucleotide Sequencing; Humans; Keratolytic Agents - therapeutic use; Male; Middle Aged; Odds Ratio; Patients; Pharmacogenomic Variants; Polymorphism; Polymorphism, Single Nucleotide; Psoriasis; Psoriasis - diagnosis; Psoriasis - drug therapy; Psoriasis - genetics; Psoriasis vulgaris; Regression analysis; Replication; Single-nucleotide polymorphism; Skin diseases; whole exome sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18020295

Psoriasis vulgaris is an immune-mediated inflammatory skin disease. Although acitretin is a widely used synthetic retinoid for moderate to severe psoriasis, little is known about patients' genetics in response to this drug. In this study, 179 patients were enrolled in either the discovery set (13 patients) or replication set (166 patients). The discovery set was sequenced by whole exome sequencing and sequential validation was conducted in the replication set by MassArray assays. Four SNPs (single nucleotide polymorphisms) (rs1105223T>C in , rs11086065A>G in , rs3821414T>C in , rs1802073 T>G in ) were found to be significantly associated with acitretin response in either co-dominant or dominant models via multivariable logistic regression analysis, while rs1105223CC (OR = 4.10, 95% CI = 1.46-11.5, = 0.007) and rs11086065AG/GG (OR = 2.76, 95% CI = 1.42-5.37, = 0.003) were associated with no response to acitretin after 8-week treatment. Meanwhile, ARHGEF3 rs3821414CT/CC (OR = 0.25, 95% CI = 0.10-0.68, = 0.006) and SFRP4 rs1802073GG/GT (OR = 2.40, 95% CI, 1.23-4.70, = 0.011) were associated with a higher response rate. Four new genetic variations with potential influences on the response to acitretin were found in this study which may serve as genetic markers for acitretin in psoriasis patients.