S. Tokgozoglu et al., Methylene tetrahydrofolate reductase genotype and the risk and extent of coronary artery disease in a population with low plasma folate, HEART, 81(5), 1999, pp. 518-522
Citations number
29
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective-To determine the effects of the thermolabile methylene tetrahydro
folate reductase (MTHFR) mutation on the presence and extent of coronary at
herosclerosis in a population with low plasma folate.
Methods-242 consecutive patients undergoing coronary angiography were prosp
ectively evaluated for conventional risk factors, plasma homocysteine, vita
min B-12, and folate, and MTHFR genotype. The severity of coronary atherosc
lerosis was determined by the Leaman score.
Results-Mean (SD) plasma homocysteine was 15.6 (10) mu mol/l in controls an
d 18.5 (11) mu mol/l in patients with coronary artery disease (p > 0.05). P
lasma homocysteine concentrations above 15 mu mol/l were a risk factor for
coronary artery disease (p = 0.03, risk ratio 2.1, 95% confidence interval
(CI) 1.07 to 4.4). Homocysteine remained an independent risk factor on mult
ivariate analysis when conventional risk factors were taken into account (p
= 0.04). Homocysteine concentrations above 15 mu mol/l were correlated wit
h the extent of atherosclerosis (p = 0.04, risk ratio 3.2, 95% CI 1.3 to 8.
2). Homocysteine had no effect on other lipid variables (p > 0.05). Plasma
folate was 15.8 (7.2) nmol/l in controls and 11.5 (2.9) nmol/l in patients
with coronary artery disease. Plasma folate concentrations below 12.9 nmol/
l (5.7 ng/ml) conferred a risk for coronary artery disease (p = 0.03, risk
ratio 2.42, 95% CI 1.05 to 5.59). When the MTHFR genotype was determined, t
he TT genotype was present in 7.4% of patients and 5.2% of controls (p > 0.
05). The prevalence of alleles was within the Hardy-Weinberg equilibrium (T
T 7, CT 40, CC 53, chi(2) = 2.3, p = 0.3) The highest homocysteine concentr
ations were found in patients with the TT genotype and folate below the med
ian of the population (p = 0.01). The extent of coronary atherosclerosis ju
dged by the Leaman score was significantly higher in patients with the TT g
enotype (p = 0.03).
Conclusions-Plasma homocysteine over 15 mu mol/l was a significant risk fac
tor for the presence and extent of coronary artery disease. The mean plasma
folate of the population was low and correlated negatively with homocystei
ne. Although TT genotype was not an independent predictor of coronary arter
y disease, it was an important predictor of the extent of coronary atherosc
lerosis and plasma homocysteine, especially in the presence of plasma folat
e values below the median of the population. These findings may have import
ant implications for folate replacement in patients with the TT genotype.