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

Abstract

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 CRB2, rs11086065A>G in ANKLE1, rs3821414T>C in ARHGEF3, rs1802073 T>G in SFRP4) were found to be significantly associated with acitretin response in either co-dominant or dominant models via multivariable logistic regression analysis, while CRB2 rs1105223CC (OR = 4.10, 95% CI = 1.46–11.5, p = 0.007) and ANKLE1 rs11086065AG/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.

The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients

“…Pharmacogenetics is a subject to explore the correlation between genetic information and drug response 46‐48 . However, few reports have been focused on the association between gene polymorphisms and MTX efficacy.…”

“…Pharmacogenetics is a subject to explore the correlation between genetic information and drug response. [46][47][48] However, few reports have been focused on the association between gene polymorphisms and MTX efficacy. Previous studies have shown that ABC transporter family members are associated with MTX efficacy, including polymorphisms in the ABCC1, and ABCG2 genes, and other genetic polymorphisms of RFC-1, 49,50 MTHFR, 51,52 ATIC, 53 FPGS 54 and FOXP3.…”

Frizzled-related proteins 4 (SFRP4) rs1802073G allele predicts the elevated serum lipid levels during acitretin treatment in psoriatic patients from Hunan, China

“…In our previous study, we found SFRP4 rs1802073 polymorphism was associated with the response to acitretin, namely, the psoriatic patients who carries T allele had a better response than that in G allele carriers ( Zhou et al, 2017 ). SFRP4 rs1802073 polymorphism is a missense mutation (G>T), and induce a proline to change into threonine at position 320 in the SFRP4 protein.…”

“…In our previous research, we showed that secreted frizzled-related proteins 4 (SFRP4) rs1802073G>T was a missense mutation and was significantly associated with the response to acitretin ( Zhou et al, 2017 ). SFRP4 is a frizzled decoy receptor that binds to Wnt/β-catenin and inhibits the Wnt/β-catenin signaling pathway, through competing surface receptors ( Carmon & Loose, 2008 ).…”

Correction: Xingchen Zhou, et al. Whole Exome Sequencing in Psoriasis Patients Contributes to Studies of Acitretin Treatment Difference. Int. J. Mol. Sci. 2017, 18, 295

“…We would like to submit the following correction to the published paper [ 1 ], the reason for this action is that the data in Table 3 were reanalyzed by one more accurate statistic method: On page 12, the sentence of paragraph three “OR and 95% CI were calculated by limited backward-LR (likelihood ratio) logistic regression analysis with adjustment by clinical variables” should be corrected into “OR and 95% CI were calculated by limited enter logistic regression analysis with adjustment by clinical variables”. The corrections resulted some changes in Table 3 and related data in text, while the significance and the conclusions remained unchanged.…”