Department of Cardiology, Suining Central Hospital, Suining, Sichuan, China.
J Cell Mol Med. 2024 Jun;28(12):e18474. doi: 10.1111/jcmm.18474.
Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
我们之前的研究认为,5,10-亚甲基四氢叶酸还原酶(MTHFR)的 rs1801133 变体对冠心病(CAD)的影响可能是通过心脏代谢紊乱介导的。本研究旨在验证这一假设。本病例对照研究纳入了 430 例 CAD 患者和 216 例 CAD 对照组。通过 PCR-RFLP 对 rs1801133 变体进行基因分型。通过狭窄冠状动脉数量和冠状动脉狭窄程度评估冠状动脉病变严重程度。rs1801133 T 等位基因显著增加了 CAD 患者和 CAD 对照组的同型半胱氨酸水平。携带 rs1801133 T 等位基因的个体患 CAD 的风险增加。相反,rs1801133 的 TT 基因型个体发生多血管病变的风险较高。携带 CT 基因型的个体的收缩压(SBP)、低密度脂蛋白胆固醇(LDL-C)和高敏 C 反应蛋白(hs-CRP)水平较高,载脂蛋白 A1(APOA1)水平较低与 CAD 男性患者的 CC 基因型相比。受试者工作特征(ROC)曲线和精确召回(PR)曲线表明,高同型半胱氨酸血症对预测 CAD 的严重程度具有敏感性。多变量逻辑回归显示,同型半胱氨酸、rs1801133、年龄、吸烟、体重、体重指数(BMI)、脂蛋白(a)[Lp(a)]和 hs-CRP 是 CAD 的独立危险因素。在中国汉族人群中,rs1801133 与 CAD 风险增加和冠状动脉病变严重程度相关,至少部分归因于高同型半胱氨酸血症。高同型半胱氨酸血症对严重 CAD 或多血管病变具有较高的预测价值。