title: Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism.
abstract: 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.
authors: Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Poland. jpazik@poczta.fm
authors: J
authors: J
authors: Pazik
authors: M
authors: M
authors: Ołdak
authors: M
authors: M
authors: Podgórska
authors: Z
authors: Z
authors: Lewandowski
authors: E
authors: E
authors: Sitarek
authors: R
authors: R
authors: Płoski
authors: J
authors: J
authors: Szmidt
authors: A
authors: A
authors: Chmura
authors: M
authors: M
authors: Durlik
authors: J
authors: J
authors: Malejczyk
mesh_terms: D000328:Adult; D000483:Alleles; D000961:Antilymphocyte Serum / Q000009:adverse effects; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D000961:Antilymphocyte Serum; D017931:DNA Primers; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human