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肝移植术后脂肪性肝病肝内代谢途径的遗传多态性。

Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation.

机构信息

Department of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

Liver Int. 2018 Dec;38(12):2287-2293. doi: 10.1111/liv.13920. Epub 2018 Jul 18.

DOI:10.1111/liv.13920
PMID:29935100
Abstract

BACKGROUND & AIMS: Fatty liver disease is an important complication associated with liver transplantation, and the cytochrome P-450 system of the donor liver may be involved in its pathogenesis. To explore the effects of the CYP27A1, CYP27B1, CYP2R1, and vitamin D receptor pathways on vitamin D maintenance after living donor liver transplantation, we investigated the interplay between serum 25(OH)D and common variants in 60 paired donors and recipients who underwent living donor liver transplantation.

METHODS

We prospectively collected 60 donor/recipient pairs from our liver transplantation programmes and extracted serum DNA to evaluate single nucleotide polymorphisms in CYP27A1 rs4674344, CYP27B1 rs10877012, CYP2R1 rs10741657, and VDR rs2228530 alleles using real-time polymerase chain reaction. We measured serum 25(OH)D concentrations of donors (D-D0) and recipients before (R-D0) and after (R-D30) living donor liver transplantation for comparison with repeated-measures analysis of variance in generalized estimating equations analysis.

RESULTS

Fatty liver disease was noted in 28.3% of the cases after living donor liver transplantation, and the graft rejection rate was 25%. There were significant differences in low serum 25(OH)D concentrations between D-D0 and R-D0 and between R-D0 and R-30 groups. Significant associations were observed for serum CYP27A1 rs4674344 in recipients and donors as well as for graft liver tissue with VDR rs2228530. There was no significant relationship with serum CYP27B1 rs10877012 in recipients and donors or with graft liver tissue with CYP2R1 rs10741657.

CONCLUSIONS

Donor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.

摘要

背景与目的

脂肪肝是肝移植的一个重要并发症,供体肝脏的细胞色素 P-450 系统可能参与其发病机制。为了探讨 CYP27A1、CYP27B1、CYP2R1 和维生素 D 受体途径对活体供肝移植后维生素 D 维持的影响,我们研究了 60 对接受活体供肝移植的供体和受者的血清 25(OH)D 与常见变异体之间的相互作用。

方法

我们前瞻性地从我们的肝移植项目中收集了 60 对供体/受者,提取血清 DNA,使用实时聚合酶链反应评估 CYP27A1 rs4674344、CYP27B1 rs10877012、CYP2R1 rs10741657 和 VDR rs2228530 等位基因的单核苷酸多态性。我们测量了供体(D-D0)和受者在活体供肝移植前(R-D0)和后(R-D30)的血清 25(OH)D 浓度,并使用广义估计方程分析的重复测量方差分析进行比较。

结果

活体供肝移植后 28.3%的病例出现脂肪肝,移植物排斥率为 25%。D-D0 和 R-D0 以及 R-D0 和 R-30 组之间的血清 25(OH)D 浓度有显著差异。受者和供体血清 CYP27A1 rs4674344 以及移植物肝组织 VDR rs2228530 有显著相关性。受者和供体血清 CYP27B1 rs10877012 以及移植物肝组织 CYP2R1 rs10741657 与无显著关系。

结论

供体/受者 CYP27A1 rs4674344 和移植物 VDR rs2228570 可能与低血清 25(OH)D 有关,可能在活体供肝移植后受者脂肪肝的发生中起主要作用。

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