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Do MDR1 and SLCO1B1 Polymorphisms Influence the Therapeutic Response to Atorvastatin? A Study on a Cohort of Egyptian Patients with Hypercholesterolemia

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Abstract

Background

Statins are among the most prescribed drugs worldwide to reduce the risk of cardiovascular events. Interindividual variability in drug response is a major clinical problem and is of concern during drug development. Statins, such as atorvastatin, are taken orally and access to their site of action in the liver is greatly facilitated by both intestinal and hepatic transporters.

Objective

To examine the impact of polymorphisms of the multidrug resistance 1(MDR1) and solute carrier organic anion transporter 1B1 (SLCO1B1) genes on the therapeutic response to atorvastatin as well as the presence of gender–gene interaction.

Methods

Serum lipid levels were determined at baseline and 4 weeks following 40 mg/day atorvastatin treatment in 50 Egyptian hypercholesterolemic patients (27 males and 23 females). Identification of MDR1 C3435T and SLCO1B1 A388G gene polymorphisms was performed using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.

Results

Treatment with atorvastatin resulted in a mean reduction of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglyceride (TG) of 8.7 %, 9.2 %, and 4.1 %, respectively, and a mean increase of high density lipoprotein cholesterol (HDL-C) of 1 %. Baseline and post-treatment HDL-C levels were statistically significantly higher in the MDR 1 TT homozygotes when compared with the CC wild type. The percentage change in TC, LDL-C, TG, and HDL-C did not show any statistically significant difference when compared among the different MDR 1 C3435T or SLCO1B1 A388G genotypes. The SLCO1B1 GG homozygotes showed a decrease in TG, whereas there was an increase in TG following atorvastatin treatment in AA and AG carriers in females; however, males did not show any statistically significant difference. There was no statistically significant association between either the coronary artery disease (CAD) risk factors (family history of CAD, hypertension, diabetes mellitus, smoking) or concomitant medications with the percentage change in different lipid parameters.

Conclusion

MDR1 C3435T was associated with baseline and post-treatment HDL-C variation. SLCO1B1 A388G showed gender-related effects on TG change following atorvastatin treatment. None of the comorbidities or the concomitant medications influenced the percentage change of lipid parameters following atorvastatin treatment. The results of this study may lead to an improved understanding of the genetic determinants of lipid response to atorvastatin treatment.

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Abbreviations

ABC:

ATP binding cassette

ANOVA:

Analysis of variance

EIPICO:

Egyptian International Pharmaceutical Industries Co.

ER:

Estrogen receptor

HDL-C:

High density lipoprotein cholesterol

LDL-C:

Low density lipoprotein cholesterol

MDR1 :

Multidrug resistance 1

OATP1B1:

Organic anion transporter polypeptide 1B1

PCR-RFLP:

Polymerase chain reaction–restriction fragment length polymorphism

P-gp:

P-glycoprotein

SLCO1B1:

Solute carrier organic anion transporter 1B1

SNP:

Single nucleotide polymorphism

TC:

Total cholesterol

TG:

Triglycerides

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Disclosure statement

The authors have no conflicts of interest that are directly relevant to the content of this article.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

    Mona F. Shabana

  2. Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Amal A. Mishriki

  3. Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, El Saray St., El Manial, 11956, Cairo, Egypt

    Marianne Samir M. Issac

  4. Department of Cardiology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Sameh W. G. Bakhoum

Authors
  1. Mona F. Shabana
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  2. Amal A. Mishriki
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  3. Marianne Samir M. Issac
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Corresponding author

Correspondence to Marianne Samir M. Issac.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. I. Agarose gel electrophoresis showing multidrug resistance 1 (MDR1) C3435 T genotypes (DOCX 49 kb)

40291_2013_38_MOESM2_ESM.docx

Supplementary Fig. II. Agarose gel electrophoresis showing solute carrier organic anion transporter 1B1 (SLCO1B1) A388G genotypes (DOCX 167 kb)

Supplementary Table I. Characteristics of the patients included in this study (DOCX 12 kb)

40291_2013_38_MOESM4_ESM.docx

Supplementary Table II. Percentage change in lipid profile after atorvastatin treatment according to patients’ characteristics and concomitant medication (DOCX 18 kb)

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Shabana, M.F., Mishriki, A.A., Issac, M.S.M. et al. Do MDR1 and SLCO1B1 Polymorphisms Influence the Therapeutic Response to Atorvastatin? A Study on a Cohort of Egyptian Patients with Hypercholesterolemia. Mol Diagn Ther 17, 299–309 (2013). https://doi.org/10.1007/s40291-013-0038-3

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