Effects of single-nucleotide polymorphisms in MTHFR and MTRR on mortality and allograft loss in kidney transplant recipients.
BACKGROUND
Plasma total homocysteine (tHcy) is associated with cardiovascular outcomes in kidney transplant recipients (KTR). The methylenetetrahydrofolate-reductase (MTHFR) 677C>T polymorphism, an important determinant of plasma tHcy concentrations, could therefore constitute an important prognostic marker.


METHODS
We prospectively followed 710 KTR over >6 years. The MTHFR677C>T, MTHFR1298A>C, MTHFR1793G>A, and MTRR66A>G polymorphisms were analyzed. Demographic, clinical, and transplant-related information was obtained, and patients were followed-up using the Austrian Dialysis and Transplant Registry. Using Cox regression, we established the independent relations of each genotype to the risk of death from any cause, and/or kidney allograft loss.


RESULTS
During a median follow-up of 6.1 years, 154 participants died and 260 kidney allografts were lost. Compared to patients with the MTHFR677CC genotype, patients with MTHFR677CT had an adjusted relative mortality risk of 1.02 (95%CI 0.70-1.47), and those with MTHFR677TT of 0.98 (95%CI 0.52-1.85). Compared to MTHFR677CC, the relative risks of kidney allograft loss were 0.93 (95%CI 0.70-1.23; MTHFR677CT) and 0.78 (95%CI 0.47-1.30; MTHFR677TT), respectively. None of the other genotypes were associated with the risks studied, either. These findings did not depend on whether we controlled for tHcy levels.


CONCLUSIONS
This study does not support the routine use of MTHFR or MTRR genotyping for prognostic evaluation or risk-stratification in kidney transplant recipients.
Winkelmayer
Wolfgang C
WC
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Boston, MA 02120, USA. wolfgang@post.harvard.edu
Kramar
Reinhard
R
Sunder-Plassmann
Gere
G
Födinger
Manuela
M
D000328:Adult; D000368:Aged; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing; D005838:Genotype; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D014184:Transplantation, Homologous
D005819:Genetic Markers; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)