Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched case-control study.
BACKGROUND
It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians.


METHODS
Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age.


RESULTS
In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11).


CONCLUSIONS
In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.
Golbahar
Jamal
J
Department of Biochemistry, Faculty of Medicine, Cardiovascular Unit, Shiraz University of Medical Sciences, Iran. golbaharj@sums.ac.ir
Rezaian
Golamreza
G
Fathi
Z
Z
Aminzadeh
Mohammad A
MA
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood*; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D013763:Tetrahydrofolates / Q000097:blood
D013763:Tetrahydrofolates; D006710:Homocysteine; D005492:Folic Acid; C005984:5-methyltetrahydrofolate