Nutrigenetic impact of daily folate intake on plasma homocysteine and folate levels in patients with different methylenetetrahydrofolate reductase genotypes.
BACKGROUND
Elevated plasma homocysteine level is associated with coronary artery disease (CAD). Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is typically but inconsistently associated with hyperhomocysteinemia. We examined the impact of daily intake of folate, a co-factor in homocysteine metabolism, on plasma homocysteine and folate levels in CAD patients in relation with MTHFR genotypes.


METHODS
Daily folate intake was assessed from 3-day food records in 99 patients with CAD: 35 with the T/T (homozygous mutant) genotype and 64 with the C/C or C/T (non-T/T) genotypes.


RESULTS
Patients with the T/T genotype had higher fasting plasma homocysteine levels (18.4±1.9 vs. 12.6±0.6 μmol/l, P=0.01) and lower plasma folate levels (17.8±1.7 vs. 20.8±1.0 nmol/l, P=0.02). There were no differences between the genotype groups in energy-adjusted folate intake. In patients with the non-T/T genotypes, higher folate intake was associated with higher plasma folate levels and lower plasma homocysteine levels. In T/T homozygotes this association was weaker. Linear regression analysis showed that folate intake, the MTHFR genotype, plasma vitamin B12 levels, and the interaction between plasma folate level and MTHFR genotype, predicted homocysteine elevation. (folate intake, P=0.04, MTHFR genotype, P=0.03, plasma folate, P=0.02, and plasma B12 level, P=0.004). The model explained only 29% of the variance in log-transformed plasma homocysteine levels.


CONCLUSIONS
T/T homozygotes are more sensitive to the combination of low folate intake, low plasma folate and vitamin B12 level, than patients with non-T/T genotypes. The variability in plasma homocysteine in T/T homozygotes is only partly explained by these variables.
Messika
Amalia Haviv
AH
Department of Cardiology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Kaluski
Dorit Nitzan
DN
Lev
Eli
E
Iakobishvili
Zaza
Z
Shohat
Mordechai
M
Hasdai
David
D
Mager
Aviv
A
D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood*; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D007557:Israel; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D054647:Nutrigenomics; D016017:Odds Ratio; D010641:Phenotype
D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)