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Biol Blood Marrow Transplant. 2012;18(1):37-43.

Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine blood levels and clinical outcomes in patients who receive allogeneic hematopoietic stem cell transplantation.

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제1저자 고영일 · 교신저자 김인호

PMID 21896346 DOI 10.1016/j.bbmt.2011.08.019 IF 3.275 혈액종양내과
소속 (1)
  1. Department of Internal Medicine, Seoul National University Hospital, Korea.

Abstract

In patients who received allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the correlations between single nucleotide polymorphisms (SNPs) in genes that regulate cyclosporine metabolism and clinical outcomes. All patients received sibling-matched HSCT. DNA samples of patients and donors were analyzed for 4 SNPs: MDR1 +1236C>T (rs1128503), +2677G>T>A (rs2032582), +3435C>T (rs1045642), and CYP3A5 +6986G>A (rs776746). A total of 156 patients (median age 40 years) were analyzed. Nineteen patients received HSCT for nonmalignant disease. The CYP3A5 +6986AA genotype was associated with a high cyclosporine blood level after transplantation. However, this genotype was not related to any particular clinical outcome. In contrast, the MDR1 +1236C>T SNP was correlated with specific clinical outcomes. When neither the donor nor the recipient had the CC genotype of MDR1 +1236, patients had lower creatinine levels (P < .001) and less transplantation-related mortality (TRM) (P = .012). These patients also showed longer overall survival (OS) in both univariate (P = .003) and multivariate (P = .003) analyses. Although the CYP3A5 +6986AA genotype was correlated with a high blood cyclosporine concentration, lack of the MDR1 +1236CC genotype in both the donor and recipient was correlated with less TRM and a longer OS in patients who received allogeneic HSCT.

Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · eISSN 1523-6536
전자 출판
2011-09-05
MeSH
ATP Binding Cassette Transporter, Subfamily B · ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics / metabolism · Adolescent · Adult · Aged · Cyclosporine / blood · Cytochrome P-450 CYP3A / genetics / metabolism · Female · Genotype · Hematopoietic Stem Cell Transplantation / methods · Humans · Male · Middle Aged · Polymorphism, Single Nucleotide · Transplantation, Homologous · Young Adult
Substances
ABCB1 protein, human · ATP Binding Cassette Transporter, Subfamily B · ATP Binding Cassette Transporter, Subfamily B, Member 1 · Cyclosporine · CYP3A5 protein, human · Cytochrome P-450 CYP3A