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Effect of ABCB1 Genotype on Pre- and Post-Cardiac Transplantation Plasma Lipid Concentrations

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Abstract

Genetic variation of ATP-binding cassette subfamily B member 1 (ABCB1) which encodes P-glycoprotein (P-gp) has been associated with lipid levels and response to statins. Here, we studied these associations in patients with advanced heart failure who subsequently underwent transplantation. Fasting total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) concentrations in 268 adult heart transplant recipients were analysed retrospectively before and at 1 year after transplantation (n = 176). ABCB1 genotyping and haplotyping for C1236T, G2677T/A and C3435T was performed using polymerase chain reaction. Pre-transplant LDL cholesterol was found to be associated with the C3435T genotype and the G2677T/A-C3435T and C1236T-G2677T/A-C3435T haplotypes. T-allele carriers at all loci (n = 77) had higher LDL levels than non-T-allele carriers (n = 24, 3.5 ± 1.2 vs. 2.8 ± 1.2 mmol/L, respectively, p = 0.025). This association remained after adjustment for age, sex, body mass index, statin use and underlying ischaemic heart disease. ABCB1 genotype was not associated with post-transplant lipid parameters. Hypercholesterolaemia (TC >5.7 mmol/L) was more prevalent post-transplant than pre-transplant (51% vs. 30%, respectively) and was likely related to steroid and calcineurin inhibitor use. Muscle-related statin effects were only seen in patients possessing the T-haplotype. In conclusion, an association between ABCB1 haplotype and plasma fasting LDL cholesterol concentration was found in patients with advanced heart failure. This association was not seen 1 year after cardiac transplantation.

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Abbreviations

ABCB1 :

ATP-binding cassette, subfamily B, member 1

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

MDR1 :

Multidrug resistance gene 1

ns:

Non-significant

PCR:

Polymerase chain reaction

SNP:

Single nucleotide polymorphism

TC:

Total cholesterol

TG:

Triglycerides

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Funding Sources

This work was supported by Magdi Yacoub Institute and the Royal Brompton, the Harefield NHS Trust Clinical Research Committee and the National Institutes of Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College.

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Authors and Affiliations

  1. Transplant Unit, Royal Brompton and Harefield NHS Trust, Harefield Hospital, London, UK

    Anne B. Taegtmeyer, Jane B. Breen, John Smith, Paula Rogers & Nicholas R. Banner

  2. Heart Science Centre, National Heart and Lung Institute, Imperial College, Harefield, Middlesex, UK

    Anne B. Taegtmeyer, Magdi H. Yacoub & Paul J. R. Barton

  3. Faculty of Medicine, Imperial College, London, UK

    Nicholas R. Banner

  4. NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK

    Paula Rogers & Paul J. R. Barton

  5. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland

    Anne B. Taegtmeyer & Gerd A. Kullak-Ublick

  6. Klinik für Klinische Pharmakologie und Toxikologie, Universitätsspital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland

    Anne B. Taegtmeyer

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  1. Anne B. Taegtmeyer
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Correspondence to Anne B. Taegtmeyer.

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Taegtmeyer, A.B., Breen, J.B., Smith, J. et al. Effect of ABCB1 Genotype on Pre- and Post-Cardiac Transplantation Plasma Lipid Concentrations. J. of Cardiovasc. Trans. Res. 4, 304–312 (2011). https://doi.org/10.1007/s12265-011-9269-z

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  • DOI: https://doi.org/10.1007/s12265-011-9269-z

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