The Association of Methylenetetrahydrofolate Reductase Gene Polymorphism with Coronary Heart Disease
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摘要:
目的 评价四氢叶酸还原酶基因(MTHFR)多态性与冠心病严重程度的相关性。 方法 研究对象为需行冠脉造影术及必要时支架植入术患者400名,行叶酸代谢677基因检测,按MTHFR C677T多态性分为 野生型C/C、纯合突变型C/T、杂合突变型T/T 3组,并行冠脉Gensini评分,随访所有行PCI患者术后180 d内发生 MACE事件(包括心脏死亡、心肌梗死、心力衰竭、心脏原因再次入院、靶血管再次血运重建)的情况。 结果 (1) MTHFR C677T T/T基因型患者冠脉Gensini评分显著高于C/T、C/C基因型患者(P < 0.05);(2) MTHFR C677T T/T基因型患者术后180 d内发生的MACE事件显著高于C/T、C/C基因型患者(P < 0.05)。 结论 (1) MTHFR多态性与冠脉病变严重程度显著相关;(2) MTHFR多态性与冠心病患者术后180 d内发生的MACE事件显著相关。 -
关键词:
- 四氢叶酸还原酶 /
- 冠脉Gensini评分 /
- PCI /
- MACE
Abstract:Objective To analyze the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and severity of coronary heart disease. Methods A total of 400 patients who were to undergo coronary angiography and stent implantation when necessary were tested with folate metabolism 677 gene. And according to MTHFR C677T polymorphism, these patients were divided into three groups: C / C, C / T, T / T and Gensini score of coronary artery was used to evaluate the mace events (including cardiac death, myocardial infarction, heart failure, readmission for cardiac reasons and target vessel revascularization) within 180 days after PCI. Results (1) Patients with MTHFR C677T T/T genotype had significantly higher Gensini scores than those with C/T and C/C genotypes (P < 0.05). (2) Patients with MTHFR C677T T/T genotype had significantly higher mace events than those with C/T and C/C genotypes after 180 days of PCI (P < 0.05). Conclusion (1) There is a significant correlation between MTHFR gene polymorphism and severity of coronary heart disease; (2) There is a significant correlation between MTHFR gene polymorphism and the mace events after 180 days of PCI. -
Key words:
- MTHFR /
- Gensini score /
- PCI /
- MACE
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表 1 三组患者的临床特征(
$\bar x \pm s $ )Table 1. Clinical features (
$\bar x \pm s $ )临床特征 野生型 CC(56例) 纯合突变型 TT(180例) 杂合突变型CT(164例) t/χ2 P 年龄(岁) 62.74 ± 9.59 62.63 ± 9.47 62.69 ± 9.56 0.69 0.42 男性[n(%)] 37(66.0) 119(66.1) 108(65.8) 0.51 0.79 糖尿病[n(%)] 18(32.1) 59(32.7) 54(32.9) 1.46 0.18 高血压[n(%)] 13(23.2) 40(22.2) 36(21.9) 1.54 0.21 吸烟[n(%)] 26(46.4) 83(46.1) 75(45.7) 2.41 0.19 心脑血管病家族史[n(%)] 31(55.3) 99(55.0) 90(54.8) 2.15 0.20 ALT(U) 36.8 ± 17.00 32.2 ± 13.50 34.2 ± 11.55 0.71 0.55 AST(U) 35.6 ± 13.00 35.8 ± 10.20 34.8 ± 11.70 0.68 0.67 Scr(μmol/L) 85.4 ± 23.05 85.9 ± 17.05 86.1 ± 16.05 0.82 0.62 TC(mmol/L) 5.36 ± 0.95 5.28 ± 0.91 5.32 ± 0.93 0.91 0.71 TG(mmol/L) 2.01 ± 0.97 2.36 ± 2.60 2.29 ± 1.74 0.70 0.58 LDL-C(mmol/L) 3.25 ± 1.11 3.15 ± 0.82 3.17 ± 0.77 0.84 0.63 HDL-C(mmol/L) 1.35 ± 0.28 1.34 ± 0.31 1.29 ± 0.43 0.91 0.72 表 2 三组患者的合并用药情况n(%)
Table 2. Combination features n(%)
合并用药 野生型 CC(56例) 纯合突变型 TT(180例) 杂合突变型CT(164例) t P 阿斯匹林 56(100) 180(100) 164(100) 1.82 0.20 氯吡格雷 45(80.3) 144(80.0) 131(79.8) 1.57 0.19 替格瑞洛 11(19.7) 36(20.0) 33(20.2) 1.90 0.24 低分子肝素 16(28.5) 54(30.0) 50(30.4) 1.74 0.20 β-受体阻滞剂 39(69.6) 126(70.0) 114(69.5) 1.91 0.24 Ⅱb/Ⅲa 6(10.7) 17(9.4) 16(9.7) 1.84 0.23 降糖药物 18(32.1) 59(32.7) 54(32.9) 1.79 0.19 ACEI/ARB 13(23.2) 39(21.6) 35(21.3) 1.88 0.22 表 3 三组患者的冠脉Gensini评分及PCI治疗情况(
$ \bar x \pm s$ )Table 3. Gensini score and PCI features (
$\bar x \pm s $ )冠脉Gensini评分PCI情况 野生型 CC(56例) 纯合突变型TT(180例) 杂合突变型CT(164例) χ2 P Gensini评分 39.86 ± 22.09 55.71 ± 20.61 49.88 ± 28.07 2.85 0.02 平均靶血管狭窄程度(%) 88.1 ± 11.3 87.3 ± 12.6 89.3 ± 11.6 1.88 0.20 平均支架直径(mm) 0.39 ± 0.41 0.41 ± 0.42 0.40 ± 0.38 1.76 0.24 平均支架长度(mm) 20.1 ± 4.70 31.9 ± 7.50 25.6 ± 3.90 2.75 0.03 表 4 PCI术后180 d内MACE n(%)
Table 4. MACE within 180 days after PCI n(%)
MACE事件 野生型 CC(43例) 纯合突变型TT(141例) 杂合突变型CT(128例) t P 心脏死亡 0(0) 2(1.4) 1(0.8) 2.13 0.24 心肌梗死 0(0) 3(2.1) 2(1.56) 2.44 0.24 心力衰竭 1(2.3) 3(2.1) 1(0.8) 2.42 0.24 心脏原因再次入院 1(2.3) 4(2.8) 2(1.56) 2.41 0.24 靶血管再次血运重建 0(0) 2(1.4) 0(0) 2.10 0.24 总MACE事件 2(4.6) 14(9.9) 6(4.7) 3.74 0.02 -
[1] Holmes M V,Newcombe P,Hubeacek J A,et al. Effect modification by population dietary folate on the association between MTHFR genotype,homocysteine,and stroke risk:A meta-analysis of genetic studies andrandomised trials[J]. Lancet,2011,37(8):584-594. [2] 张晶,丛洪良,曹路,等. 亚甲基四氢叶酸还原酶 A1298C 多态性与 高同型半胱氨酸血症的相关性[J]. 中华老年心脑血管病杂志,2017,19(11):1166-1169. doi: 10.3969/j.issn.1009-0126.2017.11.012 [3] 胡小平,刘春莲,武玲,等. MTHFR基因C677T多态性与冠心病患者血浆同型半胱氨酸和叶酸水平相关[J]. 基础医学与临床,2011,31(7):773-776. [4] 梁长流,蒋善群,彭少杰,等. MTHFR C677T基因多态性与高同型半胱氨酸型高血压关联性研究[J]. 中华疾病控制杂志,2011,15(6):480-484. [5] 葛均波, 徐永健. 内科学[M]. 8版. 北京: 人民卫生出版社, 2014: 227. [6] Steed M M,Tyagi S C. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia[J]. Antioxid Redox Signal,2011,15(7):1927-1943. doi: 10.1089/ars.2010.3721 [7] Faraci F M. Hyperhomocysteinemia:a million ways to lose control[J]. Arterioscler Thromb Vase Biol,2003,23(3):371-373. [8] Sen U,Mishra P K,Tyagi N,et a1. Homocysteine to hydrogen sulfide or hypertension[J]. Cell Biochem Biophys,2010,57(2-3):49-58. doi: 10.1007/s12013-010-9079-y [9] Antoniades C,Antonopoulos A S,Tousoulis D,et al. Homocysteine and coronary atherosclerosis:From folate fortification to the recent clinical trials[J]. Eur Heart J,2009,30(1):6-15. [10] The homocysteine studies collaboration. Homocysteine and risk of ischemic heart disease and stroke:A meta-analysis[J]. JAMA,2002,288(16):2015-2022. doi: 10.1001/jama.288.16.2015 [11] 周佳菁,袁箐,韩峻松,等. 亚甲基四氢叶酸还原酶多态性的临床 应用研究进展[J]. 医学综述,2018,24(7):1266-1272. doi: 10.3969/j.issn.1006-2084.2018.07.004 [12] 张泽丹,曾莉,谭平. 叶酸联合维生素 B12 治疗老年冠心病慢性心 力衰竭伴高同型半胱氨酸血症的疗效分析[J]. 河北医学,2018,24(2):313-317. doi: 10.3969/j.issn.1006-6233.2018.02.036 [13] BECKETT E L,MARTIN C,BOYD L,et al. Reduced plasma homocysteine levels in elderly Australians following mandatory folic acid fortification-A comparison of two cross-sectional cohorts[J]. J Nutrit & Int Metabol,2017,8(3):14-20. -