MTHFR基因单核苷酸多态性与下肢动脉粥样硬化的关系研究
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- 英文论文题名：Association between methylenetetrahydrofolate reductase gene single nucleotide polymorphisms and lower extremity atherosclerotic disease
- 论文作者：林小凤 ; 李红娜 ; 石鹤坤 ; 林雪玉 ; 陈锦珊 ; 费燕
- 英文论文作者：Lin Xiaofeng ; Li Hongna ; Shi Hekun ; Lin Xueyu ; Chen Jinshan ; Fei Yan ; Department of Pharmacy ; The 175th Hospital of PLA(Affiliated Southeast Hospital of Xiamen University)
- 年：2016
- 作者机构：解放军第175医院药学科/厦门大学附属东南医院;
- 论文关键词：下肢动脉粥样硬化 ; 亚甲基四氢叶酸还原酶基因 ; 病例对照研究 ; 多态性 ; 关联分析
- 英文论文关键词：Lower extremity atherosclerotic disease ; Methylenetetrahydrofolate reductase gene ; Case-Control Study ; Polymorphisms ; association study
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：中文
- 分类号：R543.5
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：8
- 文件大小：978k
- 原文格式：O
- 会议级别：全国
摘要
目的:研究汉族人群中亚甲基四氢叶酸还原酶(methylene-tetrahydrofolate reductase,MTHFR)基因多态性与下肢动脉粥样硬化(lower extremity atherosclerotic disease,LEAD)的相关性。方法:收集福建省闽南地区384例(LEAD者224例,健康者160例)的临床资料及外周血;LEAD检查采用踝肱指数(ABI)、趾肱指数(TBI)、多普勒彩超和其他影像学检查等手段;选取MTHFR基因rs1801133、rs1801131、rs2274976、rs4846048、rs3737966、rs1537515、rs4846049、rs3834044、rs13306561和rs3737964等10个单核苷酸多态性(single nucleotide polymorphisms,SNP)位点进行基质辅助激光解吸附电离飞行时间质谱分析质谱技术(matrix-assisted laser desorption/ionization-time offlight,MALDKTOF)的基因分型。结果:10个SNP位点均符合Hardy-Weinberg平衡;rs4846048与rs3737966等37个位点之间存在明显连锁不平衡现像(D′均大于0.9);MTHFR基因GCCTCGGAAT单倍型在LEAD和正常组的分布差异有统计学意义(P=0.02);等位基因频率的x~2检验显示rs1801131(OR=1.287)、rs4846048(OR=1.844,P=0.02)、rs3737966(OR=1.339)、rs4846049(OR=1.314)和rs3737964(OR=1.522);且rs4846048位点的趋势卡方检验(cochran-armitage trend test,TREND)、显性基因检验(Dominant gene action test,DOM)均显示LEAD与正常组之间分布频率的差异存在显著性的统计学意义(P<0.05)。结论:MTHFR基因rs1801131、rs4846048、rs3737966、rs4846049和rs3737964等5个位点可能与LEAD的易感性相关,其中rs4846048基因突变可能是LEAD致病性的危险因素之一。
Objective To analyze the association between SNP of MTHFR gene and LEAD.Methods The clinical data and peripheral blood were collected from 384 participants(224 LEAD cases and 160 normal controls)in Han population of Minnan.LEAD was detected with ankle brachial index(ABI),toe brachial index(TBI),colour doppler ultrasonic examination and other imaging study.The SNP genotypes including rs1801133,rs1801131,rs2274976,rs4846048,rs3737966,rsl537515,rs4846049.rs3834044,rsl3306561 and rs3737964 in the MTHFR gene were detected by MALDKTOF- Results The genotype distributions of these ten loci were in accordance with Hardy-Weinberg equilibrium.There were 37 obvious linkage disequilibrium such as the association between rs4846048 and rs3737966(D'>0.9).There were significant differences(P=0.02) in GCCTCGGAAT haplotypes of MTHFR gene groups between LEAD cases and normal groups.The results from chi-square test of allele frequencies suggested rsl801131(OR= 1.287),rs4846048(OR= 1.844,P=0.02),rs3737966(OR= 1.339),rs4846049(OR=1.314)和rs3737964(OR =1.522).Significant differences(P<0.05) were observed between LEAD and normal groups in Cochran- Armitage trend test and Dominant gene action test of rs4846048.Conclusions The SNP of rsl801131,rs4846048,rs3737966,rs4846049 and rs3737964 might be associated with the susceptibility of LEAD.andrs4846048 gene mutation might serve as a risk factor for LEAD in this community-based population.
Objective To analyze the association between SNP of MTHFR gene and LEAD.Methods The clinical data and peripheral blood were collected from 384 participants(224 LEAD cases and 160 normal controls)in Han population of Minnan.LEAD was detected with ankle brachial index(ABI),toe brachial index(TBI),colour doppler ultrasonic examination and other imaging study.The SNP genotypes including rs1801133,rs1801131,rs2274976,rs4846048,rs3737966,rsl537515,rs4846049.rs3834044,rsl3306561 and rs3737964 in the MTHFR gene were detected by MALDKTOF- Results The genotype distributions of these ten loci were in accordance with Hardy-Weinberg equilibrium.There were 37 obvious linkage disequilibrium such as the association between rs4846048 and rs3737966(D'>0.9).There were significant differences(P=0.02) in GCCTCGGAAT haplotypes of MTHFR gene groups between LEAD cases and normal groups.The results from chi-square test of allele frequencies suggested rsl801131(OR= 1.287),rs4846048(OR= 1.844,P=0.02),rs3737966(OR= 1.339),rs4846049(OR=1.314)和rs3737964(OR =1.522).Significant differences(P<0.05) were observed between LEAD and normal groups in Cochran- Armitage trend test and Dominant gene action test of rs4846048.Conclusions The SNP of rsl801131,rs4846048,rs3737966,rs4846049 and rs3737964 might be associated with the susceptibility of LEAD.andrs4846048 gene mutation might serve as a risk factor for LEAD in this community-based population.
引文
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[13]Liu X,Zhao LJ,Liu YJ,et al.The MTHFR gene polymorphism is associated with lean body mass but not fat body mass[J]..Hum Genet,2008,123(2):189-196.
[14]Liu P,Lu Y,ReckerRR,et al.Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women[J]..Menopause,2010,17(1):185-90.
[15]Tang W,Zhang S,Qiu H,et al.Genetic variations in MTHFR and esophageal squamous cell carcinoma susceptibility in Chinese Han population[J].Med Oncol,2014,31(5):915.
[16]Lu Q,Jiang K,Li Q,et al.Polymorphisms in the MTHFR gene are associated with breast cancer risk and prognosis in a Chinese population[J]..Tumour Biol,2015,36(5):3757-62.
[17]王春,杨海燕,尹震宇,等.老年2型糖尿病患者过氧化物酶体增殖物活化受体γ与动脉粥样硬化程度的相关分析[J].中华老年心脑血管病杂志,2015,17(9):945-948.
[2]McPherson R.Pertsemlidis A,Kavaslar N,et al.A Common Allele on Chromosome 9 Associated with Coronary Heart Disease[J].Science,2007,316:1488-1491.
[3]Kullo IJ,Leeper NJ.The Genetic Basis of Peripheral Arterial Disease Current Knowledge,Challenges,and Future Directions[J].Circ Res,2015,24,116(9):1551-60.
[4]张建陶,郝斌,杨涛,等.甲基四氢叶酸还原酶基因多态性与下肢动脉粥样硬化闭塞症[J].中国药物与临床,2008,8(1):36-38.
[5]Wu YL,Hu CY,Lu SS,et al.Association between methylenetetrahydrofolate reductase(MTHFR)C677T/A1298C polymorphisms and essential hypertension:a systematic review and meta-analysis[J].Metabolism,2014,63(12):1503-11.
[6]Somarajan BI,Kalita J,Mittal B,et al.Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients.A case-control study in a Northern Indian population[J].J Neurol Sci,2011,304(1-2):67-70.
[7]中国高血压防治指南修订委员会.2010中国高血压防治指南[J].中华高血压杂志,2011,19:701-742.
[8]Lin X,Zhang W,Lu Q,et al.Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation[J].Med Sci Monit,2016,22:341-5.
[9]Katwal AB,Dokun AO.Peripheral arterial disease in diabetes:is there a role for genetics[J].?Curr Diab Rep,2011,11(3):218-25.
[10]Cui T.MTHFR C677T mutation increased the risk of Ischemic Stroke,especially in large-artery atherosclerosis in adults:an updated meta-analysis from 38 researches and the Severity of Coronary Atherosclerosis in a Chinese Han Population[J]..Int J Neurosci,2016,126(1):10-9.
[11]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(24):6097-6098.
[12]Spiroski I,Kedev S,Antov S,et al.Association of methylenetetrahydrofolate reduetase(MTHFR-677 and MTHFR-1298)genetic poly-morphisms with occlusive artery disease and deep venousthrombosis in Macedonians[J].Croat Med J,2008,49(1):39-49.
[13]Liu X,Zhao LJ,Liu YJ,et al.The MTHFR gene polymorphism is associated with lean body mass but not fat body mass[J]..Hum Genet,2008,123(2):189-196.
[14]Liu P,Lu Y,ReckerRR,et al.Association analyses suggest multiple interaction effects of the methylenetetrahydrofolate reductase polymorphisms on timing of menarche and natural menopause in white women[J]..Menopause,2010,17(1):185-90.
[15]Tang W,Zhang S,Qiu H,et al.Genetic variations in MTHFR and esophageal squamous cell carcinoma susceptibility in Chinese Han population[J].Med Oncol,2014,31(5):915.
[16]Lu Q,Jiang K,Li Q,et al.Polymorphisms in the MTHFR gene are associated with breast cancer risk and prognosis in a Chinese population[J]..Tumour Biol,2015,36(5):3757-62.
[17]王春,杨海燕,尹震宇,等.老年2型糖尿病患者过氧化物酶体增殖物活化受体γ与动脉粥样硬化程度的相关分析[J].中华老年心脑血管病杂志,2015,17(9):945-948.