The impact of eNOS, MTR and MTHFR polymorphisms on renal graft survival in children and young adults.
BACKGROUND
The main cause of reduced long-term graft survival is chronic allograft injury. Cardiovascular risk factors such as hyperhomocysteinaemia, accumulation of asymmetric dimethylarginine, increased oxidative stress and decreased production of nitric oxide seem to play an important role. Functional polymorphisms of the endothelial isoform of nitric oxide synthase (NOS) gene cause an alteration in nitric oxide production. Nitric oxide levels, and thus oxidative stress, are also influenced by hyperhomocysteinaemia.


METHODS
We carried out a genetic analysis of endothelial nitric oxide synthase (eNOS) 894G>T, methionine synthase (MTR) 2756A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T/1298A>C in 268 renal allograft recipient/donor (D/R) matches, with respect to long-term graft survival.


RESULTS
While MTHFR 677C>T/1298A>G and MTR 2756A>G polymorphism distribution in both recipients (R) and donors (D) showed no significant difference between matches with loss of graft function and those with long-term graft survival, the frequency of the eNOS 894TT genotype of donors was significantly increased (P = 0.040) in matches with better graft survival. The multivariate analysis identified the eNOS 894 genotype and clinically acute rejection episodes as independent risk factors for graft loss (P = 0.0406 and P = 0.0093, respectively).


CONCLUSIONS
The association between eNOS 894G>T polymorphism of donors and graft survival seems to suggest a role for this gene in chronic allograft injury; however, further studies are needed to confirm this hypothesis.
Artifoni
Lina
L
Department of Paediatrics, University of Padua, Italy. lina.artifoni@unipd.it
Benetti
Elisa
E
Centi
Sonia
S
Negrisolo
Susanna
S
Ghiggeri
Gian Marco
GM
Ginevri
Fabrizio
F
Ghio
Luciana
L
Edefonti
Alberto
A
Brambilla
Caterina
C
Cagni
Nicoletta
N
Murer
Luisa
L
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006085:Graft Survival / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase