Golbahar Jamal, Rezaian Golamreza, Fathi Z, Aminzadeh Mohammad A
Department of Biochemistry, Faculty of Medicine, Cardiovascular Unit, Shiraz University of Medical Sciences, Iran.
J Vasc Res. 2005 Jul-Aug;42(4):325-30. doi: 10.1159/000086460. Epub 2005 Jun 17.
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.
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.
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).
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.
冠状动脉疾病（CAD）风险增加是否与高血浆同型半胱氨酸水平或同型半胱氨酸再甲基化途径的成分相关，例如血浆和红细胞（RBC）中的维生素B12或5-甲基四氢叶酸（5-MTHF），目前尚未完全明确。在本研究中，我们检验了这样一个假设：RBC中的5-MTHF代表个体的长期叶酸状态，可能是同型半胱氨酸再甲基化途径紊乱更可靠的标志物，并且其缺乏可能与伊朗人的CAD相关。
对200例经血管造影证实的患者以及200名年龄和性别匹配的对照者测量血浆总同型半胱氨酸（tHcy）、维生素B12以及血浆和RBC中的5-MTHF。
血浆中，病例组的tHcy水平显著高于对照组（几何平均数12.9±6.5对10.6±5.6 μmol/L，p = 0.04）。然而，对照组的RBC 5-MTHF（527.2±185.9对461.3±117.9 nmol/L，p = 0.007）和维生素B12（254.2±132.8对182.2±110.4 pmol/L，p = 0.04）显著高于患者组。RBC 5-MTHF是血浆tHcy的强有力独立预测指标（β = -0.01，p = 0.003，r2 = 0.19）。红细胞5-MTHF处于最低四分位数的受试者患CAD的患病率是最高四分位数受试者的2.5倍。当对血浆tHcy、维生素B12、高血压和高胆固醇血症进行校正后，第一四分位数中CAD与红细胞5-MTHF的关联仍然显著（优势比，OR 2.3，置信区间：1.1 - 3.9，p = 0.01）。然而，当对红细胞5-MTHF、维生素B12、高血压和高胆固醇血症进行校正后，最高四分位数中CAD与血浆tHcy之间的关联减弱且变得不显著（OR 1.27，置信区间：0.96 - 1.69，p = 0.11）。
在本研究中，CAD与低RBC 5-MTHF之间的关联强于与血浆5-MTHF和血浆tHcy水平的关联，表明RBC 5-MTHF可能是研究伊朗人同型半胱氨酸再甲基化途径紊乱的更稳定参数。
