MTHFR C677T基因多态性及同型半胱氨酸水平与高血压患者血压变异性的关系

The Relationship between MTHFR C677T Gene Polymorphism and Homocysteine Levels and Blood Pressure Variability in Hypertensive Patients

摘要: 目的：本研究探讨MTHFR基因C677T多态性及同型半胱氨酸与高血压患者血压变异性之间的关系。方法：选取2023年1月至2024年10月期间，前往青岛大学附属医院心内科就诊的101例左心室射血分数正常的原发性高血压患者。采用24动态血压检测仪分别测量患者各血压指标[24 h收缩压(SBP)、24 h舒张压(DBP)、日间平均收缩压(dSBP)、日间平均舒张压(dDBP)、夜间平均收缩压(nSBP)、夜间平均舒张压(nDBP)]、血压变异性指标[24 h收缩压变异系数(SBPV)、24 h舒张压变异系数(DBPV)、日间平均收缩压变异系数(dSBPV)、日间平均舒张压变异系数(dDBPV)、夜间平均收缩压变异系数(nSBPV)、夜间平均舒张压变异系数(nDBPV)]及特殊时间段血压指标(夜间血压下降率及清晨收缩压和舒张压)。于清晨空腹时抽取受试者静脉血样，通过全自动生化分析仪检测受试者的甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL-c)、高密度脂蛋白(HDL-c)、转氨酶、血清肌酐(Cr)和血糖(空腹) (FBG)水平，并通过PCR荧光法检测MTHFR C677T基因型。根据不同基因型，将受试者分为CC (20例)、CT (58例)和TT (23例)组，以比较各组常规生化指标、同型半胱氨酸(Hcy)及动态血压指标差异。此外，对存在叶酸代谢障碍的TT型患者，按推荐剂量服用0.8 mg/天叶酸，连续6个月后再次测量其动态血压指标，以比较应用前后的变化。结果：共纳入符合标准的原发性高血压患者，各组年龄(64.95 ± 9.88 vs. 59.93 ± 11.85 vs. 59.87 ± 7.95, P = 0.175)，性别比例(男：45% vs. 44.8% vs. 43.5%，P = 0.993)，以及甘油三酯(TG)、胆固醇(TC)等一般资料均无统计学意义(P > 0.05)。然而，与Hcy水平存在显著差异(8.09 (7.66~8.52) vs. 13.00 (11.40~13.90) vs. 21.20 (19.00~22.30), P < 0.05)。在动态血压各项均值指标中，TT组相较于CT组及CC组存在显著差异(P < 0.05)。此外，在动态血压的变异系数，以及特定时间段如夜间血压下降率与清晨血压指标方面，TT组亦显示出显著差异(P < 0.05)。结论：MTHFR C677T基因多态性与同型半胱氨酸(Hcy)水平以及动态血压均值和变化指数显著相关。

Abstract: Objective: This study aimed to explore the relationship between MTHFR gene C677T polymorphism, homocysteine, and blood pressure variability in patients with hypertension. Methods: A total of 101 patients with primary hypertension and normal left ventricular ejection fraction who visited the Department of Cardiology of the Affiliated Hospital of Qingdao University from January 2023 to October 2024 were selected. Blood pressure indicators [24-hour systolic blood pressure (SBP), 24-hour diastolic blood pressure (DBP), daytime average systolic blood pressure (dSBP), daytime average diastolic blood pressure (dDBP), nighttime average systolic blood pressure (nSBP), and nighttime average diastolic blood pressure (nDBP)], blood pressure variability indicators [24-hour systolic blood pressure variability coefficient (SBPV), 24-hour diastolic blood pressure variability coefficient (DBPV), daytime average systolic blood pressure variability coefficient (dSBPV), daytime average diastolic blood pressure variability coefficient (dDBPV), nighttime average systolic blood pressure variability coefficient (nSBPV), and nighttime average diastolic blood pressure variability coefficient (nDBPV)], and blood pressure indicators at specific time periods (nighttime blood pressure decline rate and morning systolic and diastolic blood pressure) were measured using a 24-hour ambulatory blood pressure monitor. Venous blood samples were collected from the subjects in the morning on an empty stomach, and the levels of triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), transaminases, serum creatinine (Cr), and fasting blood glucose (FBG) were detected using an automatic biochemical analyzer. The MTHFR C677T genotype was detected by PCR fluorescence method. The subjects were divided into CC (20 cases), CT (58 cases), and TT (23 cases) groups according to different genotypes to compare the differences in conventional biochemical indicators, homocysteine (Hcy), and ambulatory blood pressure indicators among the groups. In addition, for patients with TT type and folate metabolism disorders, 0.8 mg/day of folic acid was administered for 6 consecutive months, and their ambulatory blood pressure indicators were measured again to compare the changes before and after application. Results: A total of 101 patients with primary hypertension who met the criteria were included. There were no statistically significant differences in age (64.95 ± 9.88 vs. 59.93 ± 11.85 vs. 59.87 ± 7.95, P = 0.175), gender ratio (male: 45% vs. 44.8% vs. 43.5%, P = 0.993), and general data such as triglycerides (TG) and cholesterol (TC) among the groups (P > 0.05). However, there were significant differences in Hcy levels (8.09 (7.66~8.52) vs. 13.00 (11.40~13.90) vs. 21.20 (19.00~22.30), P < 0.05). In the mean values of ambulatory blood pressure indicators, the TT group showed significant differences compared with the CT group and the CC group (P < 0.05). In addition, in the variability coefficients of ambulatory blood pressure and specific time periods such as nighttime blood pressure decline rate and morning blood pressure indicators, the TT group also showed significant differences (P < 0.05). Conclusion: MTHFR C677T gene polymorphism is significantly associated with homocysteine (Hcy) levels, mean values of ambulatory blood pressure, and variability indices.