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. 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.2013年度南京军区医学科技创新课题(编号:MS098);; 解放军第175医院青年苗圃基金项目(编号:13Y015
