Association of UDP-glucuronosyltransferase 1A9 (UGT1A9) gene polymorphism with kidney allograft function.
BACKGROUND
UDP-glucuronosyltransferases (UGTs) are a group of enzymes involved in the detoxification and excretion of xeno- and endobiotics. Polymorphic variants of the UGT1A9 gene were shown to influence exposition to mycophenolate mophetil (MMF), a common immunosuppressive drug used in kidney allograft recipients. Therefore, the aim of this study was to evaluate an association between key clinical features of kidney post-transplant course in patients receiving MMF therapy and UGT1A9-2152C>T and -275 T>A SNPs, known to induce UGT1A9 gene expression and UGT1A9 98T>C, resulting in reduced enzyme activity.


METHODS
DNA was isolated from peripheral blood of kidney allograft recipients (n=103) and a control group representing the background population of Poland (n=450). Presence of the analyzed SNP was detected using the PCR restriction fragment length polymorphism (RFLP) method. Accuracy of the applied method was confirmed by DNA sequencing.


RESULTS
In patients carrying the UGT1A9-2152T and -275A minor alleles we observed a trend of increased risk of acute allograft rejection within 3 months after transplantation, but this difference was at the border of significance. However, the UGT1A9 98C allele was found to be associated with diminished estimated glomerular filtration rate (eGFR) during the first year after engraftment and transient proteinuria in the first and second month post-transplantation. This association was not observed for UGT1A9-2152C>T and -275 T>A. Our data show that transplanted kidney function may be affected in patients carrying UGT1A9 98C allele and receiving MMF.


CONCLUSIONS
Genotyping of the functional UGT1A9 SNP may be of practical use in kidney transplant recipients.
Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Poland.
Joanna
J
Pazik
Monika
M
Ołdak
Marcin
M
Dąbrowski
Zbigniew
Z
Lewandowski
Elżbieta
E
Sitarek
Marta
M
Podgórska
Ewa
E
Ważna
Rafał
R
Płoski
Jacek
J
Szmidt
Andrzej
A
Chmura
Magdalena
M
Durlik
Jacek
J
Malejczyk
D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006084:Graft Rejection / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D014184:Transplantation, Homologous; D000090264:UDP-Glucuronosyltransferase 1A9
D017931:DNA Primers; D007166:Immunosuppressive Agents; C000715591:UGT1A9 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D009173:Mycophenolic Acid