PMID- 26376376
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 94
IP  - 37
DP  - 2015 Sep
TI  - Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression 
      With Sex and ABCB1 Haplotypes.
PG  - e1315
LID - 10.1097/MD.0000000000001315 [doi]
LID - e1315
AB  - Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and 
      mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant 
      complications. AEs may result from intracellular CNI accumulation and low 
      activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single 
      nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated 
      haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 
      patients receiving tacrolimus and enteric coated mycophenolate sodium or 
      cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment 
      determined individual and composite gastrointestinal, neurologic, aesthetic, and 
      cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T 
      (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined 
      with haplotype associations computed using the THESIAS program, and evaluated by 
      immunosuppression, sex and race using multivariate general linear models. 
      Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores 
      compared with cyclosporine with association to CTT (P = 0.018) and sex 
      (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC 
      haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic 
      (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total 
      cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were 
      higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL 
      (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins 
      (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes 
      and sex were associated with extrarenal AEs. Using haplotypes, certain female 
      patients manifested more AEs regardless of CNI. Haplotype testing may identify 
      patients with greater susceptibility to AEs and facilitate CNI individualization.
FAU - Venuto, Rocco C
AU  - Venuto RC
AD  - From the Nephrology Division; Medicine, School of Medicine and Biomedical 
      Sciences (RCV, SC, NL, AG, NN, KMT); Erie County Medical Center, Buffalo, New 
      York (RCV, AG, KMT); Immunosuppressive Pharmacology Research Program, 
      Translational Pharmacology Research Core, NYS Center of Excellence in 
      Bioinformatics and Life Sciences (CJM, SEM, LMC, KMT); Pharmacy, School of 
      Pharmacy and Pharmaceutical Sciences (CJM, SEM, KMT); Biostatistics, School of 
      Public Health and Health Professions, University at Buffalo, Buffalo, New York 
      (JDC, GEW); and Department of Pharmaceutical Sciences, College of Pharmacy, 
      University of New England, Portland, Maine (DB).
FAU - Meaney, Calvin J
AU  - Meaney CJ
FAU - Chang, Shirley
AU  - Chang S
FAU - Leca, Nicolae
AU  - Leca N
FAU - Consiglio, Joseph D
AU  - Consiglio JD
FAU - Wilding, Gregory E
AU  - Wilding GE
FAU - Brazeau, Daniel
AU  - Brazeau D
FAU - Gundroo, Aijaz
AU  - Gundroo A
FAU - Nainani, Neha
AU  - Nainani N
FAU - Morse, Sarah E
AU  - Morse SE
FAU - Cooper, Louise M
AU  - Cooper LM
FAU - Tornatore, Kathleen M
AU  - Tornatore KM
LA  - eng
GR  - R21 DK077325/DK/NIDDK NIH HHS/United States
GR  - 1R21DK077325-01A2/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (ABCB1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Calcineurin Inhibitors)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics
MH  - Adult
MH  - Calcineurin Inhibitors/*adverse effects
MH  - Cross-Sectional Studies
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Immunosuppression Therapy/*adverse effects
MH  - *Kidney Transplantation
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/*adverse effects
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Sex Factors
PMC - PMC4635790
COIS- The authors have no conflicts of interest to disclose
EDAT- 2015/09/17 06:00
MHDA- 2015/12/17 06:00
PMCR- 2015/09/18
CRDT- 2015/09/17 06:00
PHST- 2015/09/17 06:00 [entrez]
PHST- 2015/09/17 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
PHST- 2015/09/18 00:00 [pmc-release]
AID - 00005792-201509030-00008 [pii]
AID - 10.1097/MD.0000000000001315 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2015 Sep;94(37):e1315. doi: 10.1097/MD.0000000000001315.