» Articles » PMID: 25172973

Possible Association of ABCB1:c.3435T>C Polymorphism with High-density-lipoprotein-cholesterol Response to Statin Treatment--a Pilot Study

Overview
Specialty General Medicine
Date 2014 Aug 31
PMID 25172973
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

The gene product ABCB1 (formerly MDR1 or P-glycoprotein) is hypothesized to be involved in cholesterol cellular trafficking, redistribution and intestinal re-absorption. Carriers of the ABCB1:3435T allele have previously been associated with decreases in ABCB1 mRNA and protein concentrations and have been correlated with changes in serum lipid concentrations. The aim of this study was to investigate possible association between the ABCB1:3435T>C polymorphism and changes in lipids in patients following statin treatment. Outpatients (n=130) were examined: 43 men (33%), 87 women (67%): treated with atorvastatin or simvastatin (all patients with equivalent dose of 20 or 40 mg/d simvastatin). Blood was taken for ABCB1:3435T>C genotyping, and before and after statin treatment for lipid concentration determination (total cholesterol, high-density-lipoprotein-cholesterol (HDL-C), triglycerides). Change (Δ) in lipid parameters, calculated as differences between measurements before and after treatment, were analyzed with multiple regression adjustments: gender, diabetes, age, body mass index, equivalent statin dose, length of treatment. Univariate and multivariate analyses showed significant differences in ΔHDL-C (univariate p=0.029; multivariate p=0.036) and %ΔHDL-C (univariate p=0.021; multivariate p=0.023) between patients with TT (-0.05 ± 0.13 g/l; -6.8% ± 20%; respectively) and CC+CT genotypes (0.004 ± 0.15 g/l; 4.1 ± 26%; respectively). Reduction of HDL-C in homozygous ABCB1:3435TT patients suggests this genotype could be associated with a reduction in the benefits of statin treatment.

Citing Articles

Insights into the genetic architecture of haematological traits from deep phenotyping and whole-genome sequencing for two Mediterranean isolated populations.

Kuchenbaecker K, Gilly A, Suveges D, Southam L, Giannakopoulou O, Kilian B Sci Rep. 2022; 12(1):1131.

PMID: 35064169 PMC: 8782863. DOI: 10.1038/s41598-021-04436-9.


An association of ABCG8: rs11887534 polymorphism and HDL-cholesterol response to statin treatment in the Polish population.

Salacka A, Boron A, Goracy I, Hornowska I, Safranow K, Ciechanowicz A Pharmacol Rep. 2021; 73(6):1781-1786.

PMID: 34173968 PMC: 8599229. DOI: 10.1007/s43440-021-00302-7.


The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial.

Leon-Cachon R, Bamford A, Meester I, Barrera-Saldana H, Gomez-Silva M, Garcia Bustos M Sci Rep. 2020; 10(1):8900.

PMID: 32483134 PMC: 7264171. DOI: 10.1038/s41598-020-65843-y.


Interactions Between Genotype and Preoperative Statin Use Impact Clinical Outcomes Among Breast Cancer Patients.

Tryggvadottir H, Huzell L, Gustbee E, Simonsson M, Markkula A, Jirstrom K Front Oncol. 2018; 8:428.

PMID: 30370250 PMC: 6194198. DOI: 10.3389/fonc.2018.00428.


Assessment of the Risk of Rhabdomyolysis and Myopathy During Concomitant Treatment with Ticagrelor and Statins.

Danielak D, Karazniewicz-Lada M, Glowka F Drugs. 2018; 78(11):1105-1112.

PMID: 30003466 PMC: 6061431. DOI: 10.1007/s40265-018-0947-x.


References
1.
Hoffmeyer S, Burk O, von Richter O, Arnold H, Brockmoller J, Johne A . Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000; 97(7):3473-8. PMC: 16264. DOI: 10.1073/pnas.97.7.3473. View

2.
Barter P, OBrien R . Achievement of target plasma cholesterol levels in hypercholesterolaemic patients being treated in general practice. Atherosclerosis. 2000; 149(1):199-205. DOI: 10.1016/s0021-9150(99)00402-5. View

3.
Jones P, Kafonek S, Laurora I, Hunninghake D . Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998; 81(5):582-7. DOI: 10.1016/s0002-9149(97)00965-x. View

4.
Hung C, Tai J, Lin C, Lee M, Liou H . Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response. Pharmacogenomics. 2005; 6(4):411-7. DOI: 10.1517/14622416.6.4.411. View

5.
Garrigues A, Escargueil A, Orlowski S . The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc Natl Acad Sci U S A. 2002; 99(16):10347-52. PMC: 124917. DOI: 10.1073/pnas.162366399. View