Association of methylenetetrahydrofolate reductase T677 allele with early development of chronic allograft nephropathy.
OBJECTIVE
The aim of this study was to evaluate the role of genetic polymorphisms on the development of chronic allograft nephropathy (CAN).


METHODS
Using the polymerase chain reaction (PCR), polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), interleukin-6 (IL-6 G-174C) and CD14 (C-260T) were evaluated in 92 kidney transplant recipients with stable renal graft function and no signs of acute rejection in a protocol that included graft biopsy at 12 months after kidney transplantation. A normal population sample (n = 365) was also included. Multivariate analysis was used to evaluate the effect of different variables on the CAN appearance.


RESULTS
There were no differences in alleles and genotypes distribution between transplant group and normal population sample. The CAN+ group (n = 69) significantly differed from CAN- (n = 23) in both MTHFR (P < 0.05) and IL-6 (P < 0.01) genotype distribution. Using logistic regression multivariate analysis, MTHFR T677 allele (OR: 3.91, CI: 1.11-13.8; P < 0.05), patient age (OR: 0.94, CI: 0.88-0.98; P < 0.01) and proteinuria (OR: 3.63, CI: 1.25-10.6; P < 0.05) were associated with CAN. Although the IL-6 G-174 allele was shown to be associated with CAN development in univariate analysis (P < 0.01), the multivariate analysis did not show an association. There was no relation between CD14 gene polymorphism and CAN.


CONCLUSIONS
The MTHFR T677 allele is associated with the presence of CAN in kidney graft biopsies 12 months after transplantation.
Viklický
Ondrej
O
Department of Nephrology, Institute for Clinical and Experimental Medicine, 14021, Prague 4, Czech Republic. ondrej.viklicky@medicon.cz
Hubácek
Jaroslav A
JA
Kvasnicka
Jan
J
Matl
Ivo
I
Voska
Ludek
L
Skibová
Jelena
J
Teplan
Vladimír
V
Vítko
Stefan
S
D000483:Alleles; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000201:enzymology / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007674:Kidney Diseases / Q000201:enzymology / Q000235:genetics*; D016030:Kidney Transplantation; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011507:Proteinuria; D014184:Transplantation, Homologous
D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)