ABCB1 Haplotypes, Sex, Calcineurin Inhibitors and Lipid Profiles Post-Renal Transplant

C. Meaney,^1,2 R. Venuto,³ D. Brazeau,⁴ J. Consiglio,⁵ L. Cooper,¹ G. Wilding,⁵ K. Tornatore.^1,2,3

¹NYS Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY
²School of Pharmacy, Buffalo, NY
³Medicine, School of Medicine, Buffalo, NY
⁴University of New England College of Pharmacy, Portland, ME
⁵Biostatistics, School of Public Health, University at Buffalo, Buffalo, NY.

Meeting: 2015 American Transplant Congress

Abstract number: B267

Keywords: Adverse effects, Immunosuppression, Lipids, P-glycoprotein

Session Information

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Purpose: Hyperlipidemia is common in renal transplant recipients (RTR) during calcineurin inhibitor (CNI) immunosuppression. P-glycoprotein (P-gp) is an efflux transporter encoded by ABCB1 that modulates lipid transport, statin response and CNI exposure with a primary variant (TTT) associated with reduced function compared to wild-type (CGC). This study evaluated ABCB1 haplotypes, sex, CNI regimen and lipid profiles among RTR.

Methods: A prospective, cross-sectional study was completed in 149 stable RTR (estimated glomerular filtration rate 51±17ml/min/1.73m2) receiving cyclosporine (CYA) and mycophenolic acid (MPA; n=82) or tacrolimus (TAC) and MPA (n=67) for ≥ 6 months. Lipid profiles were obtained after 12-hour fast. The ABCB1 single nucleotide polymorphisms (SNP): c.1236C>T (rs1128503), c.2677G>T (rs2032582), and c.3435C>T (rs1045642) were determined and haplotype associations estimated by THESIAS.

Results: Lipids are summarized (Table) by sex and CNI.

Lipids by CNI Regimen and Sex
	CYA+MPA (n=82)		TAC+MPA (n=67)
Lipid Parameter	Male (n=67)	Female (n=14)	Male (n=38)	Female (n=29)	P-value
TCH (mg/dL)	182 ± 47	223 ± 57	152 ± 48	163 ± 28	ISR: <0.001 Sex: 0.026
LDL (mg/dL)	96 ± 37	117 ± 46	76 ± 29	83 ± 26	ISR: <0.001 Sex: 0.106
HDL (mg/dL)	43 ± 19	50 ± 15	44 ± 13	58 ± 19	ISR: 0.569 Sex: <0.001
TG (mg/dL)	232 ± 217	203 ± 178	164 ± 153	112 ± 43	ISR: 0.027 Sex: 0.215

ISR=Immunosuppressive regimen Higher total cholesterol (TCH), low-density lipoprotein (LDL) and triglycerides (TG) were noted with CYA with higher TCH and high-density lipoprotein (HDL) in females. Statin therapy was used in 43% with no gender differences (p=0.864). Females with TTT had 30% higher TCH (p=0.030); 32% higher LDL (p= 0.056); 18% lower HDL (p=0.087) and 147% higher TG (p= 0.090) compared to CGC. Males with TTT variant had 22% lower HDL (p=0.065). CYA and TAC troughs were significant covariates with ABCB1 haplotypes for TCH and TG (p<0.05).

Conclusions: Hyperlipidemia during CNI immunosuppression is multifactorial and influenced by sex and ABCB1 haplotype (TTT). This finding may impact individualization strategies for post-transplant hyperlipidemia.

To cite this abstract in AMA style:

Meaney C, Venuto R, Brazeau D, Consiglio J, Cooper L, Wilding G, Tornatore K. ABCB1 Haplotypes, Sex, Calcineurin Inhibitors and Lipid Profiles Post-Renal Transplant [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/abcb1-haplotypes-sex-calcineurin-inhibitors-and-lipid-profiles-post-renal-transplant/. Accessed November 23, 2024.

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