Document Type : Original Article
Authors
1
The Graduate Program of The Pharmacology and Toxicology Department, Pharmacy College, Kerbala University, Karbala, Iraq
2
Department of Clinical Pharmacy, Pharmacy College, Kerbala University, Karbala, Iraq
3
Department of Pharmacology and Toxicology, Pharmacy College, Kerbala University, Karbala, Iraq
4
Al-Subtain University, International Branch of Tehran University of Medical Sciences, Karbala, Iraq
5
College of Medicine, Al-Ameed University, Karbala, Iraq
Abstract
Introduction: Inter-individual variability in response to atorvastatin may be influenced by genetic polymorphisms affecting drug transport. The ATP-binding cassette subfamily B member 1 (ABCB1) gene encodes P-glycoprotein, a transporter involved in the absorption, distribution, and elimination of atorvastatin. This study investigated the association of ABCB1 rs1045642 (C3435T) and rs2032582 (G2677T) polymorphisms with atorvastatin efficacy and hepatic safety in Iraqi patients with dyslipidemia.
Materials and Methods: A cross-sectional study was conducted on 150 Iraqi patients with dyslipidemia receiving atorvastatin monotherapy (40 mg/day) for at least six months and 100 healthy controls. Lipid profile parameters and liver enzyme activities were measured using standard biochemical methods. Genotyping of rs1045642 and rs2032582 was performed using allele-specific polymerase chain reaction. Associations between genotypes, lipid parameters, liver enzymes, and treatment response were analyzed.
Results: Patients with dyslipidemia exhibited significantly higher levels of triglycerides, VLDL-C, ALP, and AST, along with significantly lower HDL-C concentrations, compared with healthy controls (all p < 0.05). No significant associations were observed between rs1045642 genotypes and lipid profile parameters or achievement of the LDL-C treatment target. However, rs1045642 was significantly associated with ALT concentrations (p = 0.0152). In contrast, rs2032582 was significantly associated with treatment response (P = 0.0124), and carriers of the T allele were less likely to achieve the LDL-C target under the dominant genetic model (p = 0.0175). Furthermore, rs2032582 was significantly associated with ALP levels (p = 0.0432).
Conclusions: The ABCB1 rs2032582 polymorphism was associated with atorvastatin treatment response, whereas rs1045642 showed no significant association with lipid-lowering efficacy. Both polymorphisms were associated with selected liver enzyme parameters, suggesting a potential role in atorvastatin disposition and hepatic handling. Further large-scale studies incorporating pharmacokinetic assessments are required to confirm these findings.
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