亚甲基四氢叶酸还原酶677TT多态性与低血清维生素B12联合与冠状动脉支架内再狭窄相关。

677TT polymorphism of methylenetetrahydrofolate reductase in combination with low serum vitamin B12 is associated with coronary in-stent restenosis.

作者信息

Chung Sheng-Liang, Chiou Kuan-Rau, Charng Min-Ji

机构信息

Division of Cardiology, Department of Medicine, LoTung Poh-Ai Hospital, Yilan County, Taiwan.

出版信息

Catheter Cardiovasc Interv. 2006 Mar;67(3):349-55. doi: 10.1002/ccd.20663.

DOI:10.1002/ccd.20663

PMID:16489563

Abstract

BACKGROUND

Recent studies have shown that a common mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to a mild rise in plasma homocysteine levels and increase the incidence of coronary artery disease. Therefore, this study was designed to further investigate whether the effects of MTHFR 677 C to T mutation, plasma homocysteine, serum vitamin B12, and folate can influence restenosis after successful coronary stenting.

METHODS AND RESULTS

We investigated 260 patients each with a lesion after successful coronary stent placement. All patients received a repeated angiography after 6 months, or earlier if clinically indicated. Angiographic in-stent restenosis (ISR) was defined as >or=50% diameter stenosis at follow-up. Genotyping for MTHFR was based on a polymerase chain reaction technique. Also fasting plasma homocysteine, vitamin B12, and folate levels were measured at the same time. The ISR rate was higher among the patients with the TT genotype than in those with the non-TT genotypes (64.0% versus 32.9%, P=0.002). There was no significant difference in plasma homocysteine levels among patients with the TT genotype and patients with the non-TT genotypes (15.9+/-7.6 versus 15.5+/-6.6 micromol/L, P=0.75). However, among the patients with the TT genotype, those with higher plasma homocysteine levels (>or=12 micromol/L) demonstrated a significantly higher ISR rate (75.0% versus 33.5%, P=0.001). Logistic regression analysis revealed that the combined presence of the MTHFR TT genotype and lower than average serum vitamin B12 (>or=550 pg/mL) resulted in the most significant difference in the risk of ISR (OR=3.57, CI=1.51-8.46, P=0.004; OR=2.36, CI=1.35-4.15, P=0.003).

CONCLUSIONS

MTHFR 677TT polymorphism and low serum vitamin B12 each individually increased the risk of coronary ISR. Furthermore, the combination of these parameters resulted in a greater increase in risk.

摘要

背景

近期研究表明，亚甲基四氢叶酸还原酶（MTHFR）基因中的常见突变（核苷酸677 C→T）可能导致血浆同型半胱氨酸水平轻度升高，并增加冠状动脉疾病的发病率。因此，本研究旨在进一步调查MTHFR 677 C至T突变、血浆同型半胱氨酸、血清维生素B12和叶酸的影响是否会影响冠状动脉支架置入成功后的再狭窄。

方法与结果

我们调查了260例冠状动脉支架置入成功后有病变的患者。所有患者在6个月后接受重复血管造影，如有临床指征则提前进行。支架内再狭窄（ISR）的血管造影定义为随访时直径狭窄≥50%。MTHFR基因分型基于聚合酶链反应技术。同时还测量了空腹血浆同型半胱氨酸、维生素B12和叶酸水平。TT基因型患者的ISR率高于非TT基因型患者（64.0%对32.9%，P = 0.002）。TT基因型患者和非TT基因型患者的血浆同型半胱氨酸水平无显著差异（15.9±7.6对15.5±6.6 μmol/L，P = 0.75）。然而，在TT基因型患者中，血浆同型半胱氨酸水平较高（≥12 μmol/L）的患者ISR率显著更高（75.0%对33.5%，P = 0.001）。逻辑回归分析显示，MTHFR TT基因型与低于平均血清维生素B12（≥550 pg/mL）同时存在导致ISR风险差异最为显著（OR = 3.57，CI = 1.51 - 8.46，P = 0.004；OR = 2.36，CI = 1.35 - 4.15，P = 0.003）。