武汉地区缺血性脑卒中患者MTHFR基因多态性分布分析
|
摘要
目的:探讨武汉地区缺血性脑卒中患者亚甲基四氢叶酸还原酶(MTHFR)基因多态性的分布。方法:选取缺血性脑卒中患者167例为卒中组,健康体检者110例为对照组。通过基因芯片法检测缺血性脑卒中相关的MTHFR基因677位点,并按基因型别分为野生型(C677C)、杂合型(C677T)、纯合型(T677T)。结果:卒中组中野生型22.2%,杂合型43.1%,纯合型34.7%。与对照组相比,野生型显著减少,纯合突变型显著增多,有显著性差异(P<0.01)。不同性别脑卒中患者在MTHFR基因分型上差异无统计学意义(P>0.05)。结论:武汉地区缺血性脑卒中患者中分布有较多的纯合突变型MTHFR基因。
Objective:To analyze polymorphism distribution of methylenetetrahydrofolate reductase(MTHFR)gene in ischemic stroke patients in Wuhan. Methods: Total 167 cases of ischemic stroke patients were enrolled as stroke group, and 110 healthy cases were enrolled as control group. MTHFR genotypes were detected by the gene chip method, and for different genotypes of patients were divided into wild type(C677C), heterozygous type(C677T) and homozygous type(T677T). Results:In the stroke group, wild type accounted for 22.2%, heterozygous mutant type and homozygous mutant type accounted for 43.1%, 34.7%, respectively. Compared with the control group, the wild type was significantly reduced while the homozygous mutant was significantly increased(P<0.05). Different gender had no statistical significance in MTHFR genotype differences(P>0.05). Conclusion: There are more homozygous mutant MTHFR genes in ischemic stroke patients in Wuhan area.
Objective:To analyze polymorphism distribution of methylenetetrahydrofolate reductase(MTHFR)gene in ischemic stroke patients in Wuhan. Methods: Total 167 cases of ischemic stroke patients were enrolled as stroke group, and 110 healthy cases were enrolled as control group. MTHFR genotypes were detected by the gene chip method, and for different genotypes of patients were divided into wild type(C677C), heterozygous type(C677T) and homozygous type(T677T). Results:In the stroke group, wild type accounted for 22.2%, heterozygous mutant type and homozygous mutant type accounted for 43.1%, 34.7%, respectively. Compared with the control group, the wild type was significantly reduced while the homozygous mutant was significantly increased(P<0.05). Different gender had no statistical significance in MTHFR genotype differences(P>0.05). Conclusion: There are more homozygous mutant MTHFR genes in ischemic stroke patients in Wuhan area.
引文
[1]Almawi WY,Khan A,Al-Othman SS,et al.Case-control Study of methylenetetrahydrofolate reductase mutations and hyperhomocysteinemia and risk of stroke[J].J Stroke Cerebrovasc Dis,2009,18:407-408.
[2]Wiernicki I,Millo B,Safranow K,et al.MMP-9,homocysteine and CRP circulating levels are associated with intraluminal thrombusthickness of abdominal aortic aneurysms:new implication of the old biomarkers[J].Dis Markers,2011,31:67-74.
[3]Xie R,Jia D,Gao C,et al.Homocysteine induces procoagulant activity of red blood cells via phosphatidylserine exposure and microparticles generation[J].Amino Acids,2014,46:1 997-2 004.
[4]曾宪卿,何俊.急性脑梗死患者血浆同型半胱氨酸及相关硫醇物、叶酸、维生素B12水平变化及相关性研究[J].神经损伤与功能重建,2013,8:26-29.
[5]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南[J].中华神经科杂志,2015,48:246-257.
[6]Ghodke-Puranik Y,Puranik AS,Shintre P,et al.Folate metabolic pathway single nucleotide polymorphisms:a predictive pharmacogenetic marker of methotrexate response in Indian(Asian)patients with rheumatoid arthritis[J].Pharmacogenomics,2015,16:2019-2034.
[7]Joachim E,Goldenberg NA,Bernard TJ,et al.The methylenetetrahydrofolate reductase polymorphism(MTHFR c.677C>T)and elevated plasma homocysteine levels in a U.S.pediatric population with incident thromboembolism[J].Thromb Res,2013,132:170-174.
[8]Hultdin J,Van Guelpen B,Winkvist A,et al.Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C>T and1298A>C genotypes and haplotypes-evidence for an association with hemorrhagic stroke[J].Clin Chem Lab Med,2011,49:1 555-1 562.
[9]柳华,邱亚,刘伟,等.亚甲基四氢叶酸还原酶基因C677T多态性与川东北人群缺血性脑卒中的关联[J].西部医学,2014,26:701-706.
[10]Romero-Sánchez C,Gómez-Gutierrez A,Gómez PE,et al.C677T(RS1801133)MTHFR gene polymorphism frequency in a colombian population[J].Colomb Med(Cali),2015,46:75-79.
[11]肖湘雪,白树风.MTHFR基因多态性与脑卒中的关系研究[J].中国实验诊断学,2012,16:1311-1313.
[12]Holmes MV,Newcombe P,Hubacek JA,et al.Effect modification by population dietary folate on the association between MTHFR genotype,homocysteine,and stroke risk:a meta-analysis of genetic studies and randomised trials[J].Lancet,2011,378:584-594.
[13]Tamura Y,Inoue A,Ijiri Y,et al.Short-and long-term treatment with folic acid suppresses thrombus formation in atherogenic mice in vivo[J].Pathophysiology,2014,21:169-175.
[14]`陈忠云,高金颖,李婧,等.伴高同型半胱氨酸血症的缺血性脑卒中患者的危险因素研究[J].神经损伤与功能重建,2012,6:422-424.
[2]Wiernicki I,Millo B,Safranow K,et al.MMP-9,homocysteine and CRP circulating levels are associated with intraluminal thrombusthickness of abdominal aortic aneurysms:new implication of the old biomarkers[J].Dis Markers,2011,31:67-74.
[3]Xie R,Jia D,Gao C,et al.Homocysteine induces procoagulant activity of red blood cells via phosphatidylserine exposure and microparticles generation[J].Amino Acids,2014,46:1 997-2 004.
[4]曾宪卿,何俊.急性脑梗死患者血浆同型半胱氨酸及相关硫醇物、叶酸、维生素B12水平变化及相关性研究[J].神经损伤与功能重建,2013,8:26-29.
[5]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南[J].中华神经科杂志,2015,48:246-257.
[6]Ghodke-Puranik Y,Puranik AS,Shintre P,et al.Folate metabolic pathway single nucleotide polymorphisms:a predictive pharmacogenetic marker of methotrexate response in Indian(Asian)patients with rheumatoid arthritis[J].Pharmacogenomics,2015,16:2019-2034.
[7]Joachim E,Goldenberg NA,Bernard TJ,et al.The methylenetetrahydrofolate reductase polymorphism(MTHFR c.677C>T)and elevated plasma homocysteine levels in a U.S.pediatric population with incident thromboembolism[J].Thromb Res,2013,132:170-174.
[8]Hultdin J,Van Guelpen B,Winkvist A,et al.Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C>T and1298A>C genotypes and haplotypes-evidence for an association with hemorrhagic stroke[J].Clin Chem Lab Med,2011,49:1 555-1 562.
[9]柳华,邱亚,刘伟,等.亚甲基四氢叶酸还原酶基因C677T多态性与川东北人群缺血性脑卒中的关联[J].西部医学,2014,26:701-706.
[10]Romero-Sánchez C,Gómez-Gutierrez A,Gómez PE,et al.C677T(RS1801133)MTHFR gene polymorphism frequency in a colombian population[J].Colomb Med(Cali),2015,46:75-79.
[11]肖湘雪,白树风.MTHFR基因多态性与脑卒中的关系研究[J].中国实验诊断学,2012,16:1311-1313.
[12]Holmes MV,Newcombe P,Hubacek JA,et al.Effect modification by population dietary folate on the association between MTHFR genotype,homocysteine,and stroke risk:a meta-analysis of genetic studies and randomised trials[J].Lancet,2011,378:584-594.
[13]Tamura Y,Inoue A,Ijiri Y,et al.Short-and long-term treatment with folic acid suppresses thrombus formation in atherogenic mice in vivo[J].Pathophysiology,2014,21:169-175.
[14]`陈忠云,高金颖,李婧,等.伴高同型半胱氨酸血症的缺血性脑卒中患者的危险因素研究[J].神经损伤与功能重建,2012,6:422-424.