Association between Methylenetetrahydrofolate Reductase Gene Single Nucleotide Polymorphisms and Lower Extremity Atherosclerotic Disease
- 药学院－已发表论文 
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电离飞行时间质谱分析技术(matrix-assisted laser desorption ionization-time of flight,MALDI-TOF)的基因分型。结果:10个SNP位点均符合HardyWeinberg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χ~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χ~2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有统计学意义(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 gene single nucleotide polymorphisms( SNP) of methylenetetrahydrofolate reductase( MTHFR) gene and lower extremity atherosclerotic disease( LEAD). Methods: The clinical data and peripheral blood were collected from 384 participants( 224 LEAD cases and 160 normal controls) from Han population of Minnan Fujian. LEAD was detected with ankle brachial index( ABI),toe brachial index( TBI),color Doppler ultrasonic examination and the other imaging studies. The SNP genotypes including rs1801133,rs1801131,rs2274976,rs4846048,rs3737966,rs1537515,rs4846049,rs3834044,rs13306561 and rs3737964 in the MTHFR gene were detected by matrix-assisted laser desorption ionization-time of flight( MALDITOF). Results: The genotype distributions of the ten loci were in accordance with Hardy-Weinberg equilibrium. There were 37 obvious linkage disequilibrium,including the association between rs4846048 and rs3737966( D' > 0. 9) and so on. There were significant differences( P = 0. 02) in GCCTCGGAAT haplotypes of MTHFR gene groups between LEAD cases and the normal groups. The results from chi-square test of allele frequencies suggested rs1801131( OR = 1. 287),rs4846048( OR = 1. 844,P = 0. 02),rs3737966( OR =1. 339),rs4846049( OR = 1. 314) and rs3737964( OR = 1. 522). Significant differences( P < 0. 05) were observed between LEAD and the normal groups in Cochran- Armitage trend test and Dominant gene action test of rs4846048. Conclusion: The SNP of rs1801131,rs4846048,rs3737966,rs4846049 and rs3737964 might be associated with the susceptibility of LEAD,and rs4846048 gene mutation might serve as a risk factor for LEAD in the community-based population.