Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function
文献类型：期刊论文
| 作者 | Liu, Yuan1; Li, Lei1; Ou, Baochi1; Fan, Junwei1; Peng, Zhihai1; Zhang, Chengdong2; Yuan, Liyun3; Zhang, Tao4; , |
| 刊名 | FRONTIERS IN GENETICS
 |
| 出版日期 | 2019 |
| 卷号 | 10期号:-页码:528 |
| 关键词 | GWAS CYP3A5 exome tacrolimus FAM26F |
| ISSN号 | 1664-8021 |
| DOI | 10.3389/fgene.2019.00528 |
| 文献子类 | Article |
| 英文摘要 | After liver transplantation, the liver function of a patient is gradually restored over a period of time that can be divided into a convalescence period (CP) and a stabilizing period (SP). The plasma concentration of tacrolimus, an immunosuppressant commonly used to prevent organ rejection, varies as a result of variations in its metabolism. The effects of genetic and clinical factors on the plasma concentration of tacrolimus appear to differ in the CP and SP. To establish a model explaining the variation in tacrolimus trough concentration between individuals in the CP and SP, we conducted a retrospective, single-center, discovery study of 115 pairs of patients (115 donors and 115 matched recipients) who had undergone liver transplantation. Donors and recipients were genotyped by a genome-wide association study (GWAS) using an exome chip. Novel exons were identified that influenced tacrolimus trough concentrations and were verified with bootstrap analysis. In donors, two single-nucleotide polymorphisms showed an effect on the CP (rs1927321, rs1057192) and four showed an effect on the SP (rs776746, rs2667662, rs7980521, rs4903096); in recipients, two single-nucleotide polymorphisms showed an effect in the SP (rs7828796, rs776746). Genetic factors played a crucial role in tacrolimus metabolism, accounting for 44.8% in the SP, which was higher than previously reported. In addition, we found that CYP3A5, which is known to affect the metabolism of tacrolimus, only influenced tacrolimus pharmacokinetics in the SP. |
| 学科主题 | Genetics & Heredity |
| WOS关键词 | CYP3A5 GENOTYPE ; BLOOD-CONCENTRATIONS ; DONOR ; PHARMACOGENETICS ; TRANSPLANTATION ; CALCINEURIN ; RECIPIENTS ; SIROLIMUS |
| 语种 | 英语 |
| WOS记录号 | WOS:000470234600001 |
| 出版者 | FRONTIERS MEDIA SA |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1305]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Hepatobiliary Pancreat Surg, Shanghai, Peoples R China; 2.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China; 4.Guangzhou Med Univ, Affiliated Hosp 2, Dept Organ Transplant, Guangzhou, Guangdong, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Liu, Yuan,Li, Lei,Ou, Baochi,et al. Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function[J]. FRONTIERS IN GENETICS,2019,10(-):528. |
| APA | Liu, Yuan.,Li, Lei.,Ou, Baochi.,Fan, Junwei.,Peng, Zhihai.,...&,.(2019).Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function.FRONTIERS IN GENETICS,10(-),528. |
| MLA | Liu, Yuan,et al."Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function".FRONTIERS IN GENETICS 10.-(2019):528. |
入库方式： OAI收割
来源：上海营养与健康研究所
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