The interaction between MTHFR 677 C-->T genotype and folate status is a determinant of coronary atherosclerosis risk.
The 677 C-->T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene interacts with folate status in determining elevated total plasma levels of homocysteine, a risk factor for coronary atherosclerotic disease (CAD). The present study had the following goals: 1) to define the 677 C-->T genotype-specific threshold values of both plasma and RBC folate, associated with hyperhomocysteinemia (>15 micro mol/L); and 2) to determine the risk of CAD among subjects with levels of folate below the genotype-specific threshold considered at risk for hyperhomocysteinemia. We examined 655 subjects, with (433) or without (222) angiographically documented CAD. The MTHFR 677 C-->T genotype-specific threshold values of plasma folate corresponded to the 40th, 30th and 10th percentile in the TT, CT and CC genotype, respectively. A multivariate logistic regression analysis showed that the risk of CAD among subjects with plasma folate levels below the genotype-specific thresholds was 1.6 (95% CI, 1.04-2.46). Similar results were obtained when RBC folate was considered as a measure of folate status (odds ratio = 1.8, 95% CI, 1.03-3.15). A gene-nutrient interaction that defines a higher risk for CAD is determined by folate levels below specific thresholds, which differ depending on the MTHFR 677 C-->T genotype.
Department of Clinical and Experimental Medicine, Institute of Biology and Genetics, University of Verona, Policlinico G.B. Rossi, 37134 Verona, Italy. domenico.girelli@univr.it
Domenico
D
Girelli
Nicola
N
Martinelli
Francesca
F
Pizzolo
Simonetta
S
Friso
Oliviero
O
Olivieri
Chiara
C
Stranieri
Elisabetta
E
Trabetti
Giovanni
G
Faccini
Elisa
E
Tinazzi
Pier Franco
PF
Pignatti
Roberto
R
Corrocher
D001483:Base Sequence; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D012307:Risk Factors
D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)