土家族脑卒中患者MTHFR、MTRR67基因单核苷酸多态性及其与血清同型半胱氨酸水平的关系
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摘要
目的探讨土家族亚甲基四氢叶酸还原酶(MTHFR)基因677、1298位点及蛋氨酸合成酶还原酶(MTRR)基因66位点单核苷酸多态性(SNP)及其与血清同型半胱氨酸水平的关系。方法选取土家族脑卒中住院患者92例作为卒中组,同期140例土家族健康体检人群作为对照组。采用PCR法检测两组MTHFR基因677、1298位点及MTRR基因66位点SNP及基因型,高效液相色谱法检测血浆同型半胱氨酸水平。比较MTHFR基因677、1298位点及MTRR基因66位点不同基因型脑卒中患者同型半胱氨酸水平,分析MTHFR、MTRR基因上述位点SNP与脑卒中的关系。结果两组MTHFR基因677位点CC、TT、CT基因型及C、T等位基因,1298位点CC、AA、AC基因型及C、A等位基因分布比较差异无统计学意义(P均>0.05);与对照组相比,卒中组MTRR基因66位GG基因型比率上升,AG基因型比率下降(χ~2分别为15.13、5.58,P均<0.05)。MTHFR基因677位点TT基因型同型半胱氨酸水平高于CC、CT型(P均<0.05)。MTHFR基因677、1298位点及MTRR基因66位点SNP与脑卒中发生无明显相关性(P均>0.05)。结论土家族脑卒中患者MTRR基因66位点GG基因型比率上升,AG基因型比率下降;MTHFR基因677位点TT基因型与脑卒中患者高同型半胱氨酸水平有关。
Objective To explore the single nucleotide polymorphisms(SNPs) of methylenetetrahydrofolate reductase gene 677 and 1298 loci(MTHFR677, MTHFR1298), and methionine synthase reductase gene locus 66(MTRR66)and their relationships with the serum homocysteine levels in Tujia patients with stroke.Methods Ninety-two Tujia stroke patients were selected as the stroke group, and 140 Tujia healthy subjects in the department of health management were selected as the control group. The SNPs and genotypes of MTHFR677, MTHFR1298, and MTRR 66 were detected by PCR, and the plasma homocysteine level was detected by high performance liquid chromatography(HPLC) in the two groups. The levels of homocysteine in stroke patients with different genotypes of MTHFR677, MTHFR1298, and MTRR66 were compared, and the correlation between MTHFR and MTRR SNPs and stroke was analyzed. Results The MTHFR677 CC, TT, CT genotypes and C, T allele, MTHFR1298 CC, AA, AC genotypes and C, A allele distribution were not statistically different between the two groups(all P>0.05). Compared with the control group, the ratio of GG genotype of MTRR66 in the stroke group increased significantly, while AG genotype decreased(χ~2=15.13 and 5.58, both P<0.05). The homocysteine level in patients with MTHFR677 TT genotype was higher than that of patients with CC and CT genotypes(all P<0.05). The SNPs of MTHFR677, MTHFR1298 and MTRR66 were not significantly correlated with the stroke(all P>0.05). Conclusion The ratio of the MTRR66 GG genotype in Tujia stroke patients increases and the ratio of AG genotype decreases, and the TT genotype of MTHFR677 is associated with high homocysteine levels in stroke patients.
Objective To explore the single nucleotide polymorphisms(SNPs) of methylenetetrahydrofolate reductase gene 677 and 1298 loci(MTHFR677, MTHFR1298), and methionine synthase reductase gene locus 66(MTRR66)and their relationships with the serum homocysteine levels in Tujia patients with stroke.Methods Ninety-two Tujia stroke patients were selected as the stroke group, and 140 Tujia healthy subjects in the department of health management were selected as the control group. The SNPs and genotypes of MTHFR677, MTHFR1298, and MTRR 66 were detected by PCR, and the plasma homocysteine level was detected by high performance liquid chromatography(HPLC) in the two groups. The levels of homocysteine in stroke patients with different genotypes of MTHFR677, MTHFR1298, and MTRR66 were compared, and the correlation between MTHFR and MTRR SNPs and stroke was analyzed. Results The MTHFR677 CC, TT, CT genotypes and C, T allele, MTHFR1298 CC, AA, AC genotypes and C, A allele distribution were not statistically different between the two groups(all P>0.05). Compared with the control group, the ratio of GG genotype of MTRR66 in the stroke group increased significantly, while AG genotype decreased(χ~2=15.13 and 5.58, both P<0.05). The homocysteine level in patients with MTHFR677 TT genotype was higher than that of patients with CC and CT genotypes(all P<0.05). The SNPs of MTHFR677, MTHFR1298 and MTRR66 were not significantly correlated with the stroke(all P>0.05). Conclusion The ratio of the MTRR66 GG genotype in Tujia stroke patients increases and the ratio of AG genotype decreases, and the TT genotype of MTHFR677 is associated with high homocysteine levels in stroke patients.
引文
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[12] Song Y, Li B, Wang C, et al. Association between 5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism and risk of ischemic stroke: a meta analysis[J]. J Stroke Cerebrovasc Dis, 2016,25(3):679-687.
[13] Sarecka-Hujar B, Kopyta I, Pienczk-Reclawowicz K, et al. The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls[J]. Mol Biol Rep, 2012,39(8):7957-7963.
[14] Wang X, Cheng S, Brophy VH, et al. A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations association of lymphotoxin-alpha in nonhypertensive patients[J]. Stroke, 2009,40(3):683-695.
[15] 董长颖,王铁兵,徐蕾.吉林地区汉族人群 MTHFR 基因 A1298C 多态性及与脑血管病的相关性[J].中国老年学杂志, 2013,33(2):6097-6098.
[16] Escobedo J, Emmanuel Paz-Aragon E, Vega-Rodriguez LH, et al. The methylenetetrahydrofolate reductase C677T(rs1801133)and apolipolipolrotein A5-1131T>C(rs662799) polymorphisms, and anemia are independent risk factors for ischemic stroke[J]. J Stroke Cerebrovascul Dis, 2018,27(5):1357-1362.
[17] Fan SJ, Yang BY, Zhi XY, et al. Are MTHFR C677T and MTRRA66G polymorphisms associated with overweight /obesity risk from acase-control to a meta-analysis of 30,327 subjects[J]. Int J Mol Sci, 2015,16(6):11849-11863.
[18] Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C>T polymorphism and risk of coronary heart disease [J]. JAMA, 2002,288(16):2023-2031.
[19] 安海莲,吴兆洋,吴光,等.延边地区朝鲜族和汉族人群MTRRA66G基因多态性与脑梗死的关系[J].山东医药,2016,56(42):46-68.
[2] Bogiatzi C, Hackam DG, Mcleod AI, et al. Secular trends in ischemic stroke subtypes and stroke risk factor[J]. Stroke, 2014,15(45):3208-3213.
[3] Ansari R, Mahta A, Mallack E, et al. Hyperhomocysteinemia and neurologic disorders: a review[J]. J Clin Neurol, 2014,10(4):281-288.
[4] Tofflli G, De Mattia E. Pharmacogenetic relevance of MTHFR polymorphismw[J]. Pharmacogenomics, 2008,9(9):1195-1206.
[5] Song Y, Li B, Wang C, et al. Association between 5, 10-Methylenetetrahydrofolate reductase C677T gene polymorphism and risk of ischemic stroke: a Meta-analysis[J]. J Stroke Cerebrovasc Dis, 2016,25(3):679-687.
[6] Peamukarso DT, Faradz SM, Sari S, et al. Association between methylenetetrahydrofolate reductase(MTHFR) polymorphism and carotid intima medial theickness progression in post ischaemic stroke patient[J]. Ann Transl Med, 2015,3(21):324-327.
[7] 任燕,何玉红,曹敏娟.MTHFR 与 MTRR 基因相关突变与 H 型高血压相关性分析[J].延安大学学报,2018,16(3):73-76.
[8] Bhargava S, Ali A, Parakh R, et al. Higher incidence of C677T polymorphism of the MTHFR gene in North Indian patients with vascular disease[J]. Vascular, 2012,20(2):88-95.
[9] 张婷,谢渊,李毅,等.贵州3个民族亚甲基四氢叶酸还原酶基因的遗传多态性[J].重庆医学,2013,10(42):3413-3415.
[10] Yao YS, Chang WW, Jin YL, et al. An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with ischemic stroke[J]. Gene, 2013,528(2):84-92.
[11] Kumar A, Misra S, Sagar R, et al. Relationship between factor V leiden gene variant and risk of ischemic stroke: a Case-Control Study[J]. Ann Indian Acad Neurol, 2017,20(3):284-288.
[12] Song Y, Li B, Wang C, et al. Association between 5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism and risk of ischemic stroke: a meta analysis[J]. J Stroke Cerebrovasc Dis, 2016,25(3):679-687.
[13] Sarecka-Hujar B, Kopyta I, Pienczk-Reclawowicz K, et al. The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls[J]. Mol Biol Rep, 2012,39(8):7957-7963.
[14] Wang X, Cheng S, Brophy VH, et al. A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations association of lymphotoxin-alpha in nonhypertensive patients[J]. Stroke, 2009,40(3):683-695.
[15] 董长颖,王铁兵,徐蕾.吉林地区汉族人群 MTHFR 基因 A1298C 多态性及与脑血管病的相关性[J].中国老年学杂志, 2013,33(2):6097-6098.
[16] Escobedo J, Emmanuel Paz-Aragon E, Vega-Rodriguez LH, et al. The methylenetetrahydrofolate reductase C677T(rs1801133)and apolipolipolrotein A5-1131T>C(rs662799) polymorphisms, and anemia are independent risk factors for ischemic stroke[J]. J Stroke Cerebrovascul Dis, 2018,27(5):1357-1362.
[17] Fan SJ, Yang BY, Zhi XY, et al. Are MTHFR C677T and MTRRA66G polymorphisms associated with overweight /obesity risk from acase-control to a meta-analysis of 30,327 subjects[J]. Int J Mol Sci, 2015,16(6):11849-11863.
[18] Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C>T polymorphism and risk of coronary heart disease [J]. JAMA, 2002,288(16):2023-2031.
[19] 安海莲,吴兆洋,吴光,等.延边地区朝鲜族和汉族人群MTRRA66G基因多态性与脑梗死的关系[J].山东医药,2016,56(42):46-68.