中青年急性心肌梗死与MTHFR基因多态性及血浆Hcy水平的相关性
|
摘要
目的探讨中青年人急性心肌梗死(AMI)与亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy)水平的相关性。方法选择2017年3月至2018年6月接受治疗的中青年AMI患者95例及同期体检的健康者88例为研究对象。采集研究对象空腹静脉血进行检测,收集血清检测叶酸、维生素B_(12)(VitB_(12))、血尿酸(UA)水平,收集血浆测定Hcy水平,提取白细胞中基因组DNA,检测MTHFR基因C677T位点的多态性;采用Spearman法对MTHFR基因多态性及Hcy水平进行相关性分析,对影响AMI的因素进行Logistic回归分析。结果心肌梗死组高血压比例、高血糖比例及Hcy水平高于对照组,UA、VitB_(12)及叶酸水平低于对照组(P<0.05,P<0.01)。两组基因型分布有显著统计学差异(P<0.01),心肌梗死组T/T基因型比例最高,对照组C/T基因型比例最高;心肌梗死组的C等位基因频率低于对照组,T等位基因频率高于对照组(P<0.05);在对照组中T/T基因型的Hcy水平显著高于C/C基因型(P<0.05);心肌梗死组中Hcy水平呈T/T基因型>C/T基因型>C/C基因型(P<0.05)。Spearman相关性分析结果显示,MTHFR基因C677T位点多态性与Hcy水平显著相关(r=0.689,P=0.000),调整年龄、性别、BMI、吸烟史、饮酒、血压等影响因素后,MTHFR基因C677T多态性与Hcy水平有相关性(r=0.645,P=0.000);Logistic回归分析结果显示,高血压、高血糖、高Hcy水平均是影响AMI的独立危险因素,而UA、VitB_(12)、叶酸均是AMI的保护因素,血浆高Hcy水平患者的AMI发病风险是血浆Hcy正常者的2.336倍。结论中青年人AMI与MTHFR基因C677T的多态性、血清Hcy水平升高均密切相关,其均是导致AMI的危险因素。
Objective To investigate the associations of methylenetetrahydrofolate reductase(MTHFR) gene polymorphism and plasma homocysteine(Hcy) level with young and middle-aged acute myocardial infarction(AMI).Methods Ninety-five young and middle-aged AMI patients(AMI group) treated from March 2017 to June 2018 and 88 healthy people(control group) at the same time were selected as the subjects.Fasting venous blood was collected for serum detection of folic acid,vitamin B_(12)(VitB_(12)) and uric acid(UA) and plasma detection of Hcy.Genomic DNA was extracted from white blood cells,and MTHFR gene C677T locus polymorphism was detected.Spearman method was used to analyze the correlation between MTHFR gene polymorphism and Hcy level.Logistic regression analysis was used to analyze the influencing factors of AMI.Results The proportion of patients with hypertension and hyperglycemia in AMI group was significantly higher than those in control group(P<0.05,P<0.01).Compared with control group,the levels of UA,VitB_(12) and folic acid decreased,and the level of Hcy increased significantly in AMI group(P<0.05,P<0.01).There were significant differences in genotypes between the two groups(P<0.01).The proportion of T/T genotype was highest in MI group and the C/T genotype was highest in the control group.C allele frequency in AMI group was significantly lower and T allele frequency was significantly higher than that in control group(P<0.05).In control group,Hcy level of T/T genotype was significantly higher than that of C/C genotype(P<0.05).Hcy levels in AMI group were T/T genotype>C/T genotype>C/C genotype(P<0.05).Spearman correlation analysis showed that MTHFR gene polymorphism was correlated with Hcy level(r=0.689,P=0.000).After adjusting for age,sex,BMI,smoking history,alcohol consumption and blood pressure,the correlation between them remained(r=0.645,P=0.000).Logistic regression analysis showed that hypertension,hyperglycemia and high Hcy level were the independent risk factors of AMI,while UA,VitB_(12) and folic acid were the protective factors for AMI patients,and the risk of AMI in patients with high plasma Hcy level was 2.336 times higher than that in persons with normal plasma Hcy level.Conclusion Young and middle-aged AMI is closely related to MTHFR gene C677T polymorphism and elevated serum Hcy level,and both of them are the risk factors for AMI.
Objective To investigate the associations of methylenetetrahydrofolate reductase(MTHFR) gene polymorphism and plasma homocysteine(Hcy) level with young and middle-aged acute myocardial infarction(AMI).Methods Ninety-five young and middle-aged AMI patients(AMI group) treated from March 2017 to June 2018 and 88 healthy people(control group) at the same time were selected as the subjects.Fasting venous blood was collected for serum detection of folic acid,vitamin B_(12)(VitB_(12)) and uric acid(UA) and plasma detection of Hcy.Genomic DNA was extracted from white blood cells,and MTHFR gene C677T locus polymorphism was detected.Spearman method was used to analyze the correlation between MTHFR gene polymorphism and Hcy level.Logistic regression analysis was used to analyze the influencing factors of AMI.Results The proportion of patients with hypertension and hyperglycemia in AMI group was significantly higher than those in control group(P<0.05,P<0.01).Compared with control group,the levels of UA,VitB_(12) and folic acid decreased,and the level of Hcy increased significantly in AMI group(P<0.05,P<0.01).There were significant differences in genotypes between the two groups(P<0.01).The proportion of T/T genotype was highest in MI group and the C/T genotype was highest in the control group.C allele frequency in AMI group was significantly lower and T allele frequency was significantly higher than that in control group(P<0.05).In control group,Hcy level of T/T genotype was significantly higher than that of C/C genotype(P<0.05).Hcy levels in AMI group were T/T genotype>C/T genotype>C/C genotype(P<0.05).Spearman correlation analysis showed that MTHFR gene polymorphism was correlated with Hcy level(r=0.689,P=0.000).After adjusting for age,sex,BMI,smoking history,alcohol consumption and blood pressure,the correlation between them remained(r=0.645,P=0.000).Logistic regression analysis showed that hypertension,hyperglycemia and high Hcy level were the independent risk factors of AMI,while UA,VitB_(12) and folic acid were the protective factors for AMI patients,and the risk of AMI in patients with high plasma Hcy level was 2.336 times higher than that in persons with normal plasma Hcy level.Conclusion Young and middle-aged AMI is closely related to MTHFR gene C677T polymorphism and elevated serum Hcy level,and both of them are the risk factors for AMI.
引文
[1] 王翠,韦福起.中青年急性心肌梗死危险因素分析[J].西南军医,2008,10(4):74-75.
[2] 仝淑花,胡俊青,唐彪,等.急性心肌梗死患者NT-proBNP与HCY检测临床意义[J].浙江中西医结合杂志,2014,24(2):97.
[3] 霍勇,徐希平.依靠我国循证医学证据,更加安全有效预防脑卒中——H型高血压防治的现状和展望[J].中国医学前沿杂志(电子版),2011,3(3):4-9.
[4] Frosst P,Blom HJ,Milos R,et al.A candidate genetic risk factor for vascular disease:a common mutation in methylenetetrahydrofolate reductase[J].Nat Genet,1995,10(1):111-113.
[5] 李蕊,杨柳,苏明权,等.MTHFR基因多态性及血浆同型半胱氨酸水平与心脑血管疾病的相关性分析[J].检验医学,2016,31(10):922-924.
[6] 中华医学会心血管病学分会,中华心血管病杂志编辑委员会,《中国循环杂志》编辑委员会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,29(12):710-725.
[7] 苏懿,王磊,张敏州.急性心肌梗死的流行病学研究进展[J].中西医结合心脑血管病杂志,2012,10(4):467-469.
[8] 周浩,魏守超,赵兴军,等.5,10-亚甲基四氢叶酸还原酶基因多态性与脑梗死患者颈动脉粥样硬化的相关性研究[J].中国卒中杂志,2017,27(1):23-28.
[9] 徐鹏,何飞,王军.短暂性脑缺血发作与血清胱抑素C和同型半胱氨酸水平的相关性探讨[J].内科急危重症杂志,2014,20(4):271-272.
[10] 王利军,牛小媛,琚小红,等.MTHFR基因多态性及血浆同型半胱氨酸水平与中青年人脑梗死的关系[J].中风与神经疾病杂志,2006,23(4):478-481.
[11] 章志玲,张明,张淑华.同型半胱氨酸浓度及MTHFR基因多态性与急性心肌梗死的相关性分析[J].当代医学,2016,22(22):36-38.
[12] 蒋萍,臧大维.急性脑梗死患者MTHFR基因多态性与血浆同型半胱氨酸水平的关系[J].山东医药,2014,54(8):1-4,8.
[13] Hou XH,Huang YM,Mi YY.Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer:an updated meta-analysis[J].Asian Pac J Cancer Prev,2012,13(5):2025-2029.
[14] 章志玲,张明,葛郁芝.MTHFR基因多态性与急性心肌梗死的相关性分析[J].中国心血管病研究,2017,15(9):801-803.
[15] Yilmaz MI,Stenvinkel P,Sonmez A,et al.Vascular health,systemic inflammation and progressive reduction in kidney function;clinical determinants and impact on cardiovascular outcomes[J].Nephrol Dial Transplant,2011,26(11):3537-3543.
[16] Kluijtmans LA,Kastelein JJ,Lindemans J,et al.Thermolabile me-thylenetetrahydrofolate reductase in coronary artery disease[J].Circulation,1997,96(8):2573-2577.
[17] Ventura P,Venturelli G,Marcacci M,et al.Hyperhomocysteinemia and MTHFR C677T polymorphism in patients with portal vein thrombosis complicating liver cirrhosis[J].Thromb Res,2016,141:189.
[18] 邵大荣,孟治木,武华,等.MTHFR C677T与缺血(出血)性脑卒中风险相关性评估[J].安徽医学,2016,37(4):393-397.
[19] 秦韶阳,黄山,张春阳.MTHFR基因C677T多态性与心血管疾病相关性的Meta分析[J].分子诊断与治疗杂志,2017,9(1):6.
[2] 仝淑花,胡俊青,唐彪,等.急性心肌梗死患者NT-proBNP与HCY检测临床意义[J].浙江中西医结合杂志,2014,24(2):97.
[3] 霍勇,徐希平.依靠我国循证医学证据,更加安全有效预防脑卒中——H型高血压防治的现状和展望[J].中国医学前沿杂志(电子版),2011,3(3):4-9.
[4] Frosst P,Blom HJ,Milos R,et al.A candidate genetic risk factor for vascular disease:a common mutation in methylenetetrahydrofolate reductase[J].Nat Genet,1995,10(1):111-113.
[5] 李蕊,杨柳,苏明权,等.MTHFR基因多态性及血浆同型半胱氨酸水平与心脑血管疾病的相关性分析[J].检验医学,2016,31(10):922-924.
[6] 中华医学会心血管病学分会,中华心血管病杂志编辑委员会,《中国循环杂志》编辑委员会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,29(12):710-725.
[7] 苏懿,王磊,张敏州.急性心肌梗死的流行病学研究进展[J].中西医结合心脑血管病杂志,2012,10(4):467-469.
[8] 周浩,魏守超,赵兴军,等.5,10-亚甲基四氢叶酸还原酶基因多态性与脑梗死患者颈动脉粥样硬化的相关性研究[J].中国卒中杂志,2017,27(1):23-28.
[9] 徐鹏,何飞,王军.短暂性脑缺血发作与血清胱抑素C和同型半胱氨酸水平的相关性探讨[J].内科急危重症杂志,2014,20(4):271-272.
[10] 王利军,牛小媛,琚小红,等.MTHFR基因多态性及血浆同型半胱氨酸水平与中青年人脑梗死的关系[J].中风与神经疾病杂志,2006,23(4):478-481.
[11] 章志玲,张明,张淑华.同型半胱氨酸浓度及MTHFR基因多态性与急性心肌梗死的相关性分析[J].当代医学,2016,22(22):36-38.
[12] 蒋萍,臧大维.急性脑梗死患者MTHFR基因多态性与血浆同型半胱氨酸水平的关系[J].山东医药,2014,54(8):1-4,8.
[13] Hou XH,Huang YM,Mi YY.Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer:an updated meta-analysis[J].Asian Pac J Cancer Prev,2012,13(5):2025-2029.
[14] 章志玲,张明,葛郁芝.MTHFR基因多态性与急性心肌梗死的相关性分析[J].中国心血管病研究,2017,15(9):801-803.
[15] Yilmaz MI,Stenvinkel P,Sonmez A,et al.Vascular health,systemic inflammation and progressive reduction in kidney function;clinical determinants and impact on cardiovascular outcomes[J].Nephrol Dial Transplant,2011,26(11):3537-3543.
[16] Kluijtmans LA,Kastelein JJ,Lindemans J,et al.Thermolabile me-thylenetetrahydrofolate reductase in coronary artery disease[J].Circulation,1997,96(8):2573-2577.
[17] Ventura P,Venturelli G,Marcacci M,et al.Hyperhomocysteinemia and MTHFR C677T polymorphism in patients with portal vein thrombosis complicating liver cirrhosis[J].Thromb Res,2016,141:189.
[18] 邵大荣,孟治木,武华,等.MTHFR C677T与缺血(出血)性脑卒中风险相关性评估[J].安徽医学,2016,37(4):393-397.
[19] 秦韶阳,黄山,张春阳.MTHFR基因C677T多态性与心血管疾病相关性的Meta分析[J].分子诊断与治疗杂志,2017,9(1):6.