Whole Exome Sequencing in Psoriasis Patients Contributes to Studies of Acitretin Treatment Difference.
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 inCRB2, rs11086065A>G inANKLE1, rs3821414T>C inARHGEF3, rs1802073 T>G inSFRP4) were found to be significantly associated with acitretin response in either co-dominant or dominant models via multivariable logistic regression analysis, whileCRB2rs1105223CC (OR = 4.10, 95% CI = 1.46-11.5,p= 0.007) andANKLE1rs11086065AG/GG (OR = 2.76, 95% CI = 1.42-5.37,p= 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,p= 0.006) and SFRP4 rs1802073GG/GT (OR = 2.40, 95% CI, 1.23-4.70,p= 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.
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. zhouxingchen117@163.com.|Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. zhouxingchen117@163.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. zhouxingchen117@163.com.
Xingchen
X
Zhou
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. yijing.he@foxmail.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. yijing.he@foxmail.com.
Yijing
Y
He
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. yh_927@126.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. yh_927@126.com.
Yehong
Y
Kuang
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. xylijie@medmail.com.cn.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. xylijie@medmail.com.cn.
Jie
J
Li
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. leozjl1010@126.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. leozjl1010@126.com.
Jianglin
J
Zhang
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. chenmingliang@medmail.com.cn.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. chenmingliang@medmail.com.cn.
Mingliang
M
Chen
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. lanchen2008@163.com.|Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. lanchen2008@163.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. lanchen2008@163.com.
Wangqing
W
Chen
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. sujuanderm@csu.edu.cn.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. sujuanderm@csu.edu.cn.
Juan
J
Su
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. shuangxy@sina.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. shuangxy@sina.com.
Shuang
S
Zhao
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. liupanpan91@hotmail.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. liupanpan91@hotmail.com.
Panpan
P
Liu
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. mollychen249821543@163.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. mollychen249821543@163.com.
Menglin
M
Chen
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. shenmx1988@gmail.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. shenmx1988@gmail.com.
Minxue
M
Shen
Institute of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. chenxp74@hotmail.com.
Xiaoping
X
Chen
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. zhuwu70@hotmail.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. zhuwu70@hotmail.com.
Wu
W
Zhu
Department of Dermatology, XiangYa Hospital, Central South University, Changsha 410008, China. chenxiangck@126.com.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008, China. chenxiangck@126.com.
Xiang
X
Chen
D017255:Acitretin / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000483:Alleles; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007641:Keratolytic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*
D007641:Keratolytic Agents; D017255:Acitretin
acitretin; genetic variation; psoriasis; whole exome sequencing