Association between ABCB1 (multidrug resistance transporter) genotype and post-liver transplantation renal dysfunction in patients receiving calcineurin inhibitors.
Association between ABCB1 (multidrug resistance transporter) genotype and post-liver transplantation renal dysfunction in patients receiving calcineurin inhibitors.
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DOI：
10.1097/00008571-200311000-00002
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发表时间：
2003-11-01
期刊：
影响因子：
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通讯作者：
Thummel, Kenneth E.
中科院分区：
文献类型：
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作者：
Hebert, Mary F.;Dowling, Amy L. S.;Thummel, Kenneth E.
目的：肾功能障碍是长期使用钙调神经磷酸酶抑制剂（CNI）治疗的常见且昂贵的不良后果。我们进行了一项回顾性病例对照研究，以测试接受 CNI 的肝移植患者肾功能障碍的风险是否与编码 P-糖蛋白的基因 (ABCB1) 的外显子 21 的 2677G>T 颠换有关。总共有 120 名非西班牙裔白人患者接受了评估。结果：移植后第 3 年肾功能不全的总体发生率为 40%。与携带 2677GG 基因型的患者相比，携带 ABCB1 2677TT 基因型的患者肾功能障碍的发生率降低。具有杂合子基因型的受试者的表型与 2677GG 组相似。将具有 2677TT 基因型的受试者与具有 2677GG、TG、AT 或 AG 基因型的受试者组合组进行比较，得出优势比为 0.26 (0.09-0.77)。当受试者按性别分层时，与具有不同基因型的男性相比，具有 ABCB1 2677TT 基因型的男性肾功能障碍的发生率降低。女性也获得了类似的比值比，但没有达到显着性。当 18 名手术前 SCr 浓度升高的受试者被排除在第 3 年分析之外时，与基因型组相比，其余队列中 2677TT 基因型与慢性肾功能不全之间的关联得到加强。结论：基于这些结果，我们得出结论，ABCB1 2677T (S893) 等位基因的纯合性与接受含有 CNI 的免疫抑制方案的肝移植患者慢性肾功能障碍风险降低相关。
Objective: Renal dysfunction is a common and costly adverse outcome of long-term treatment with calcineurin inhibitors (CNIs). We conducted a retrospective, case-control study to test whether the risk of renal dysfunction in liver transplantation patients receiving CNIs is associated with the 2677G>T transversion in exon-21 of the gene (ABCB1) encoding P-glycoprotein. A total of 120 non-Hispanic white patients were evaluated. Results: The overall incidence of renal dysfunction by year 3 post-transplantation was 40%. The frequency of renal dysfunction was reduced among patients with an ABCB1 2677TT genotype, as compared to those with a 2677GG genotype. Subjects with a heterozygote genotype behaved phenotypically like the 2677GG group. Comparing those subjects with a 2677TT genotype to the combined group of subjects with a 2677GG, TG, AT, or AG genotype resulted in an odds ratio of 0.26 (0.09-0.77). When subjects were stratified by gender, the frequency of renal dysfunction was reduced among men with an ABCB1 2677TT genotype, relative to men with different genotypes. A similar odds ratio was obtained for women, but it did not achieve significance. When 18 subjects with an elevated SCr concentration just prior to surgery were excluded from the year 3 analysis, the association between the 2677TT genotype and chronic renal dysfunction in the remaining cohort was strengthened comparing genotype groups. Conclusions: Based on these results, we conclude that homozygosity for the ABCB1 2677T (S893) allele is associated with reduced risk of chronic renal dysfunction among liver transplantation patients receiving an immunosuppressive regimen containing CNIs.