纤维蛋白原基因β启动子区多态性与特发型下肢深静脉血栓的相关性研究  

Association of genetic polymorphisms in the FGB promoter region with idiopathic deep venous thrombosis

作　　者：韩胜斌[1] 董坚[1] 金辉[1] 杨斌[1] 尹芳[1] 王友礼[1] 

机构地区：[1]昆明医科大学第一附属医院血管外科,云南650032

出　　处：《中华普通外科杂志》2015年第4期272-275,共4页Chinese Journal of General Surgery

基　　金：云南省科技计划面上项目基金资助项目（2010ZC123）

摘　　要：目的探寻纤维蛋白原基因β（fibrinogen gene β，FGB）启动子区可能存在的单核苷酸多态性（single nucleotide polymorphism，SNP），并揭示其对特发型下肢深静脉血栓（idiopathic deep venous thrombosis，IDVT）的影响。方法前瞻眭研究IDVT组及健康对照组各120例。对受试者纤维蛋白原BB启动子区完整测序及限制性长度多态性法（restriction fragment length polymorphsm，RFLP）双重检测，探寻可能存在的SNP并行Hardy—Weinberg遗传平衡度检验、连锁不平衡分析；最后，比较2组基因型频率并进行多因素Logistic回归分析。结果FGB启动子区存在6种SNP，即-148C／T，-249C／T，-455G／A，-854G／A，-993C／T和-1420G／A；-993C／T与-455G／A（r2=0．699）、-993C／T与-148C／T（r2=0．509）、-455G／A与-148C／T（r^2=0．556）之间存在较强的连锁不平衡关系；2组-148C／T、-249C／T、-455G／A和-1420G／A的基因型频率差异均有统计学意义（均P〈0．05）。结论纤维蛋白原每增加1个U，IDVT的发病风险相应增加4．579倍；-148T、-455G、-1420A等位基因是IDVT的危险因素；-993C／T可能通过与-455G／A、-148C／T的连锁不平衡方式对IDVT易感性产生间接影响。Objective To probe the association between possible single nucleotide polymorphism （SNP） in the FGB promoter region and idiopathic deep venous thrombosis. Methods A prospective analysis was performed in both IDVT group and control group （120 cases each ） followed by a duplex examination using gene sequencing technique and restriction fragment length polymorphism （RFLP） in the promoter region of fibrinogen gene β. Possible SNPs in this region were detected arranged before Hardy- Weinberg equilibrium test and Linkage disequilibrium （LD） analyses. Ultimately, we compared the genotype frequencies between the two groups and undertook a multiple Logistic regression. Results Six kinds of SNPs were determined in the promoter region of β-fibrinogen gene： -148C/T, -249C/T, -455G/A, -854G/A, -993C/T and -1420G/A. A stronger linkage disequilibrium was confirmed between -993C/T and -455G/A （ rz = 0. 699） ;-993C/T and -148C/T （ r2 = 0. 509） ;-455G/A and -148C/T （ r^2 = 0. 556）. Statistical differences of genotype frequencies between two groups were observed in -148C/T, -249C/T, -455G/A and -1420G/A polymorphisms （ all P 〈 0. 05 ）. Conclusions The risk of IDVT was 4. 579 times higher with every 1 g/L increase of fibrinogen concentration. Allele -148T, 455G and -1420A are IDVT risk factors. -993C/T may indirectly affect IDVT through linkage disequilibrium with 455G/A and -148C/T.

关 键 词：静脉血栓形成 纤维蛋白原 多态性 单核苷酸 LOGISTIC模型 启动区 遗传 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]