title: Effect of ABCB1 genotype on pre- and post-cardiac transplantation plasma lipid concentrations.
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.
authors: Transplant Unit, Royal Brompton and Harefield NHS Trust, Harefield Hospital, London, UK. annebarbara.taegtmeyer@usz.ch
authors: Anne B
authors: AB
authors: Taegtmeyer
authors: Jane B
authors: JB
authors: Breen
authors: John
authors: J
authors: Smith
authors: Paula
authors: P
authors: Rogers
authors: Gerd A
authors: GA
authors: Kullak-Ublick
authors: Magdi H
authors: MH
authors: Yacoub
authors: Nicholas R
authors: NR
authors: Banner
authors: Paul J R
authors: PJ
authors: Barton
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006333:Heart Failure / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008131:London; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007166:Immunosuppressive Agents; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol