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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 investigate the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and lower extremity atherosclerotic disease (LEAD) in Chinese Han population. Methods: The clinical data and peripheral blood samples of 384 cases (224 cases of LEAD and 160 cases of healthy) in Fujian Minnan area were collected. The LEAD examination was performed with ankle brachial index (ABI), toe brachial index (TBI), Doppler ultrasound and other Imaging examination and other means; 10 single nucleotide polymorphisms (SNP) sites of MTHFR gene rs1801133, rs1801131, rs2274976, rs4846048, rs3737966, rs1537515, rs4846049, rs3834044, rs13306561 and rs3737964 were selected for matrix-assisted Genotyping by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). Results: All 10 SNPs were in accordance with HardyWeinberg equilibrium. There were obvious linkage disequilibrium among 37 loci such as rs4846048 and rs3737966 (D ’> 0.9). Distribution of MTHFR gene GCCTCGGAAT haplotype in LEAD and normal group (OR = 1.287); rs4846048 (OR = 1.844, P = 0.02); rs3737966 (OR = 1.339); rs4846049 (OR = 1.314) and rs3737964 (OR = 1.522). The trend χ ~ 2 test (TREND) and Dominant gene action test (DOM) of rs4846048 showed that there was no significant difference between LEAD and normal group The distribution frequency of the difference was statistically significant (P <0.05). CONCLUSION: Five sites of MTHFR rs1801131, rs4846048, rs3737966, rs4846049 and rs3737964 may be associated with susceptibility to LEAD. The mutation of rs4846048 may be one of the risk factors for the pathogenicity of LEAD.