Pharmacogenomics and personalized medicine · 2020
Altered Gene Expression in Acne Vulgaris Patients Treated by Oral Isotretinoin: A Preliminary Study.
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Jiang Yuchen, Chen Haiyan, Han Le, Xie Xiaoyuan, Zheng Yue, Lai Wei
Аннотация
BACKGROUND/OBJECTIVE: The role of gene expression changes in acne patients treated by oral isotretinoin (ISO) and in influencing the ISO therapeutic effects is still unclear. In this study, we investigated the gene profiles of patients with severe acne who responded variously to ISO therapy.
METHODS: The peripheral blood of 113 acne vulgaris patients (Pillsbury IV grade) was collected before treatment. After 8 weeks of oral ISO, nine acne patients were selected and divided into the following groups. A: effectively treated by ISO, group B: ineffectively treated by ISO, group C: ISO-induced acne flare-up, and 3 healthy subjects were included as control group D. The peripheral blood of patients pre- and post-treatment was subjected to high-throughput RNA sequencing technology and bioinformatics analysis of the separate groups (n = 3). The candidate genes were validated by qRT-PCR.
RESULTS: Comparing pre- and post-oral ISO treatment, gene expression was changed as 39 genes in ISO-effective group, 345 genes in ISO-ineffective group, and 57 genes in ISO-induced acne flare-up group. Comparing the ISO-induced acne flare-up group with healthy control subjects revealed 34 upregulated genes and 23 downregulated genes, while comparing the ISO-induced acne flare-up group with ISO-ineffective patients identified 1835 changed genes. Expression of GATA2 (2.73 fold, P=0.024512), C4BPA (35.87 folds, P=0.038073), and CCR5 (2.48 folds, P=0.004681) increased in the ISO-induced acne flare-up patients. Meanwhile, the expression of DEFA3 (0.18 fold, P=0.041934), ELANE (0.14 fold, P=0.030767), MMP9 (0.41 fold, P=0.013383), and RPS4Y1 (0.00018 fold, P=0.000986) decreased when compared with ISO-ineffective patients.
CONCLUSION: Oral ISO treatment could temporarily alter gene expression in acne patients. ISO therapeutic mechanisms were involved, not only in regulating the inflammatory reaction but also in the process of DNA repair. GATA2, C4BPA, CCR5, DEFA3, ELANE, MMP9, and RPS4Y1 might be susceptible to genes that could participate in the ISO-induced aggravation of acne.
METHODS: The peripheral blood of 113 acne vulgaris patients (Pillsbury IV grade) was collected before treatment. After 8 weeks of oral ISO, nine acne patients were selected and divided into the following groups. A: effectively treated by ISO, group B: ineffectively treated by ISO, group C: ISO-induced acne flare-up, and 3 healthy subjects were included as control group D. The peripheral blood of patients pre- and post-treatment was subjected to high-throughput RNA sequencing technology and bioinformatics analysis of the separate groups (n = 3). The candidate genes were validated by qRT-PCR.
RESULTS: Comparing pre- and post-oral ISO treatment, gene expression was changed as 39 genes in ISO-effective group, 345 genes in ISO-ineffective group, and 57 genes in ISO-induced acne flare-up group. Comparing the ISO-induced acne flare-up group with healthy control subjects revealed 34 upregulated genes and 23 downregulated genes, while comparing the ISO-induced acne flare-up group with ISO-ineffective patients identified 1835 changed genes. Expression of GATA2 (2.73 fold, P=0.024512), C4BPA (35.87 folds, P=0.038073), and CCR5 (2.48 folds, P=0.004681) increased in the ISO-induced acne flare-up patients. Meanwhile, the expression of DEFA3 (0.18 fold, P=0.041934), ELANE (0.14 fold, P=0.030767), MMP9 (0.41 fold, P=0.013383), and RPS4Y1 (0.00018 fold, P=0.000986) decreased when compared with ISO-ineffective patients.
CONCLUSION: Oral ISO treatment could temporarily alter gene expression in acne patients. ISO therapeutic mechanisms were involved, not only in regulating the inflammatory reaction but also in the process of DNA repair. GATA2, C4BPA, CCR5, DEFA3, ELANE, MMP9, and RPS4Y1 might be susceptible to genes that could participate in the ISO-induced aggravation of acne.