CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin

Maslub MG 1 , Daud NAA 2 , Radwan MA 3 , Sha'aban A 4 , Ibrahim AG 5

Affiliations 

  • 1 Clinical Pharmacy/Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City, 11829, Cairo, Egypt. mohammed-maslub@eru.edu.eg
  • 2 School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia
  • 3 Clinical Pharmacy/Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City, 11829, Cairo, Egypt
  • 4 Division of Population Medicine, Cardiff University, Cardiff, Wales, CF14 4YS, UK
  • 5 Cardiology Department, Faculty of Medicine, Helwan University, Helwan City, 11795, Cairo, Egypt
Eur J Med Res, 2024 Nov 10;29(1):539.
PMID: 39523378 DOI: 10.1186/s40001-024-02109-7

Abstract

BACKGROUND: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians.

OBJECTIVE: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.

METHODS: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.

RESULTS: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P 

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