Pazik J, Ołdak M, Podgórska M, Lewandowski Z, Sitarek E, Płoski R, Szmidt J, Chmura A, Durlik M, Malejczyk J
Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Poland.
Transplant Proc. 2011 Oct;43(8):2943-5. doi: 10.1016/j.transproceed.2011.08.037.
Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme for de novo synthesis of guanine nucleotides, is required for lymphocyte proliferation. Inhibition of IMPDH by mycophenolic acid (MPA) constitutes part of an immunosuppressive therapy in kidney allograft recipients. The 3757T>C polymorphic variant (rs11706052) of the IMPDH2 gene, which encodes 1 of 2 IMPDH isoenzymes, has been associated with increased IMPDH activity and reduced ability of MPA to exert antiproliferative effects on lymphocytes. The association of IMPDH2 3757T>C SNP with posttransplant courses of kidney allograft recipients remains unclear. Therefore, the aim of the present study was to evaluate associations between this single nucleotide polymorphism and common posttransplant complications among Polish kidney allotransplant recipients. We observed that the frequency of IMPDH2 3757C allele in this group (n=177) did not differ significantly from a control cohort representing the background population of Poland (n=550). There were no significant differences between patients carrying the IMPDH2 3757CT and TT genotypes with respect to acute rejection risk, neutropenia, or incidences of serious infections or gastrointestinal side effects. However, we noted that the 3757C allele was associated with higher lymphocyte counts and a reduced incidence of lymphopenia among kidney allograft recipients. Our findings may be of practical significance to tailor immunosuppressive regimens in kidney transplant recipients.
肌苷单磷酸脱氢酶（IMPDH）是鸟嘌呤核苷酸从头合成的限速酶，是淋巴细胞增殖所必需的。霉酚酸（MPA）对IMPDH的抑制作用是肾移植受者免疫抑制治疗的一部分。IMPDH2基因的3757T>C多态性变体（rs11706052）编码两种IMPDH同工酶之一，与IMPDH活性增加以及MPA对淋巴细胞发挥抗增殖作用的能力降低有关。IMPDH2 3757T>C单核苷酸多态性与肾移植受者移植后的病程之间的关联尚不清楚。因此，本研究的目的是评估这种单核苷酸多态性与波兰肾移植受者常见移植后并发症之间的关联。我们观察到该组（n=177）中IMPDH2 3757C等位基因的频率与代表波兰背景人群的对照组（n=550）没有显著差异。携带IMPDH2 3757CT和TT基因型的患者在急性排斥风险、中性粒细胞减少症或严重感染或胃肠道副作用的发生率方面没有显著差异。然而，我们注意到3757C等位基因与肾移植受者中较高的淋巴细胞计数和较低的淋巴细胞减少症发生率相关。我们的发现可能对调整肾移植受者的免疫抑制方案具有实际意义。
