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Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in

Venil N Sumantran1, Pratik Mishra2, Rakesh Bera3

  • 1Department of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamil Nadu 600095, India. venil.sumantran@gmail.com.

Pharmaceutics
|February 23, 2016
PubMed

Insights

Inflammation alters skin drug metabolism by affecting cytochrome P450 (CYP450) genes. Psoriasis up-regulates some CYP450 genes, while melanoma down-regulates them, impacting drug efficacy and safety.

Area of Science:

  • Pharmacogenomics and Cutaneous Biology
  • Biochemistry and Molecular Biology
  • Dermatology and Oncology

Background:

  • Cytochrome P450 (CYP450) enzymes are crucial for drug metabolism and personalized medicine, but their expression varies between individuals.
  • Inflammation can significantly alter CYP450 expression, affecting drug efficacy and potentially leading to adverse drug-drug interactions.
  • The impact of inflammation on CYP450 gene expression in skin, particularly in dermatological conditions like melanoma and psoriasis, remains poorly understood.

Purpose of the Study:

  • To investigate the differential expression of CYP450 genes in response to inflammation in skin diseases.
  • To identify specific CYP450 genes that are altered in melanoma and psoriasis.
  • To explore the potential of these altered CYP450 genes as therapeutic targets in dermatological conditions.

Main Methods:

  • Analysis of seven publicly available microarray datasets.
  • Identification of differentially expressed genes in skin samples from patients with melanoma and psoriasis.
  • Comparison of gene expression patterns related to drug metabolism, vitamin, and lipid turnover.

Main Results:

  • Psoriasis samples showed up-regulation of genes involved in vitamin D, vitamin A, and cholesterol metabolism (e.g., CYP27B1, CYP24A1, ALDH1A3, AKR1B10, CYP7B1).
  • Melanoma samples exhibited down-regulation of genes involved in vitamin A and cholesterol metabolism (e.g., AKR1C3, CYP39A1).
  • Both diseases displayed reduced drug-metabolizing capacity due to down-regulation of CYP1B1 and CYP3A5, with melanoma showing a more pronounced loss due to CYP3A4 down-regulation.

Conclusions:

  • Inflammation in skin diseases like psoriasis and melanoma leads to distinct alterations in CYP450 gene expression.
  • Specific up-regulated genes in psoriasis (CYP24A1, CYP4F22, SULT2B1, CYP7B1) represent potential therapeutic targets.
  • Diminished drug-metabolizing capacity in both conditions, particularly in melanoma, highlights the need for careful drug selection and dosage adjustments.
Keywords:
CYP450drug metabolismmelanomamicroarraypersonalized medicinepsoriasis

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