MTHFR基因单核苷酸多态性与下肢动脉粥样硬化的关联研究

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GCCTCG-GAAT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χ2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χ2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.