Interplay between methylenetetrahydrofolate reductase gene polymorphism 677C-->T and serum folate levels in determining hyperhomocysteinemia in heart transplant recipients.
BACKGROUND
Homocysteine metabolism is often impaired in heart transplant recipients, and increased total homocysteine plasma levels may constitute a risk factor for the development of heart allograft vascular disease. Although 677C-->T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population, it is unclear whether MTHFR polymorphism influences homocysteine metabolism after heart transplant.


METHODS
Homocysteine, serum folate, renal function, concentrations of cyclosporine and its metabolites, and MTHFR genotype were determined in 57 heart transplant recipients (age, 55 +/- 11 yr; 21% women; time from transplant, 48 +/- 42 months).


RESULTS
Forty nine percent of the study population presented with hyperhomocysteinemia. Homocysteine was 17.1 +/- 5.9 micromol/liter, 19.4 +/- 4.9 micromol/liter, and 26.3 +/- 14.2 micromol/liter for genotypes CC, CT, and TT, respectively (p = 0.028, Kruskal-Wallis test). At multivariate analysis, MTHFR genotype was independently associated with homocysteine (p = 0.005). When the study population was divided into 2 groups accordingly to serum folate levels (above/below the median value of 6.1 ng/ml), MTHFR genotype remained a significant predictor of homocysteine only in patients with low serum folate (p = 0.048).


CONCLUSIONS
This study demonstrates that hyperhomocysteinemia is frequent in heart transplant recipients and that the 677C-->T transition in the MTHFR gene independently and unfavorably influences homocysteine metabolism in this group of patients. Adequate folate intake may overcome genetic predisposition to hyperhomocysteinemia.
Potena
L
L
Institute of Cardiovascular Diseases, Bologna, Italy.
Grigioni
F
F
Viggiani
M
M
Magnani
G
G
Sorbello
S
S
Falchetti
E
E
Sassi
S
S
Mantovani
V
V
Bacchi-Reggiani
L
L
Magelli
C
C
Branzi
A
A
D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D016027:Heart Transplantation / Q000502:physiology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000235:genetics*; D007677:Kidney Function Tests; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011183:Postoperative Complications / Q000175:diagnosis* / Q000201:enzymology; D011379:Prognosis; D012307:Risk Factors
D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)