Varnell Charles D, Fukuda Tsuyoshi, Kirby Cassie L, Martin Lisa J, Warshaw Barry L, Patel Hiren P, Chand Deepa H, Barletta Gina-Marie, Van Why Scott K, VanDeVoorde Rene G, Weaver Donald J, Wilson Amy, Verghese Priya S, Vinks Alexander A, Greenbaum Larry A, Goebel Jens, Hooper David K
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Pediatr Transplant. 2017 Nov;21(7). doi: 10.1111/petr.13033. Epub 2017 Sep 4.
MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.
霉酚酸酯（MMF）常用于肾移植术后，但白细胞减少症使其应用变得复杂。了解介导此风险的遗传学因素将有助于临床医生安全使用MMF。我们评估了284例21岁以下患者MMF相关白细胞减少症的发生率和病程，并进行了一项候选基因关联研究，比较了MMF相关白细胞减少症患者与对照组之间26个单核苷酸多态性（SNP）的频率。我们根据诱导治疗、类固醇使用时间、种族、中心和年龄对病例进行匹配。我们还评估了诱导治疗和SNP对所有病例发生白细胞减少症时间的影响。68例（24%）患者出现MMF相关白细胞减少症，其中59例同意进行基因分型，38例与对照组匹配。在匹配对中，没有SNP与白细胞减少症相关。在非淋巴细胞清除诱导治疗中，UGT2B7 - 900A>G（rs7438135）与MMF相关白细胞减少症风险增加相关（P = 0.038）。不同诱导药物的患者发生白细胞减少症的时间没有差异，但肌苷一磷酸脱氢酶1（IMPDH1）中的2个SNP（rs2228075，rs2278294）与发生白细胞减少症的时间延长相关。MMF相关白细胞减少症在移植后很常见。UGT2B7可能影响白细胞减少症风险，尤其是在未进行淋巴细胞清除诱导治疗的患者中。IMPDH1可能影响移植后白细胞减少症的病程。
