Combination of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene polymorphisms as determinant risk factors for chronic allograft dysfunction.
OBJECTIVE
The aim of this study was to investigate the frequency of gene angiotensin-converting enzyme insertion/deletion (ACE I/D) and methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) variants, as well as to evaluate the plasma homocysteine concentrations in 217 patients who underwent renal transplantation at least 12 months prior to define risk factors for chronic allograft dysfunction.


METHODS
The presence of the polymorphism ACE deletion was assessed by polymerase chain reaction (PCR) analysis. MTHFR polymorphisms were determined by PCR and restriction fragment length polymorphism (RFPL) techniques. The restriction enzymes were Hinf I and Mbo II for MTHFR variants C677T and A1298C, respectively. Plasma homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry (LS-MS/MS).


RESULTS
Hyperhomocysteinemias were more common in patients with chronic allograft dysfunction (P = .004). No statistically significant differences were observed between the allelic and genotypic distributions of MTHFR and ACE polymorphisms. An effective risk factor was found when the polymorphisms of the ACE and MTHFR genes and hyperhomocysteinemia were associated (odds ratio 2.51; 95% confidence interval 1.19-5.28). In conclusion, our study identified that the presence of hyperhomocysteinemia in combination with unfavorable genotypes contributes to an increased risk for development of chronic allograft dysfunction.
de Alvarenga
M P S
MP
Department of Molecular Biology, Medical School São José do Rio Preto, UNICAMP Campinas, São Paulo, Brazil. mpaula@famerp.br
Pavarino-Bertelli
E C
EC
Abbud-Filho
M
M
Ferreira-Baptista
M A S
MA
Haddad
R
R
Eberlin
M N
MN
Goloni-Bertollo
E M
EM
D000328:Adult; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000145:classification*; D012307:Risk Factors; D014184:Transplantation, Homologous
D003404:Creatinine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A