摘要
目的:抗凝血酶抵抗是世界上新发现的一种严重遗传性易栓症,其分子基础在于凝血酶原基因发生功能增强型突变。此类突变在日本(p.Arg596Leu)和塞尔维亚(p.Arg596Gln)的3个静脉血栓栓塞症家族中报道,而在世界其他地区包括中国是否存在以及是否常见尚不明确。本研究旨在探讨p.Arg596Leu、p.Arg596Gln以及抗凝血酶抵抗在我国静脉血栓栓塞症人群是否存在。方法:选择60例未知原因易栓症患者对凝血酶原基因功能区测序;采用限制性内切酶HpaⅡ对p.Arg596Leu和p.Arg596Gln突变在1 304例和1 334例病例-对照人群中进行检测;利用生物信息学工具对p.Arg596Leu和p.Arg596Gln以及其他凝血酶原基因变异分析同源性以及可能的危害。结果:在60例易栓症患者中检测到3种基因变异c.494C>T,c.316+36G>A和c.423-7G>C,微小等位基因频率均大于0.1,且预测均无功能改变;相反p.Arg596Leu和p.Arg596Gln预测为在各物种高度保守,但所有静脉血栓栓塞症患者中均未检测到这2种突变。结论:我国p.Arg596Leu和p.Arg596Gln突变可能极罕见,遗传性抗凝血酶抵抗不是我国华中地区易栓症的常见因素。
Objective：Antithrombin resistance is a severe type of hereditary thrombophilia newly discovered in the world,which is caused by gain-of-function mutations in the prothrombin gene.These type of mutations have been reported in 3pedigrees of Japan（p.Arg596Leu）and Serbia（p.Arg596Gln）,while the existence and frequency of which still remain unclear in other parts of the world including China.We set out to investigate whether antithrombin resistance is common in the population of central China.Method：Sixty unprovoked thrombophilic patients were selected for prothrombin gene re-sequencing.Mutations p.Arg596 Leu and p.Arg596 Gln were detected using a RFLP method with HpaⅡamong the study populations,including 1 304 venous thromboembolism patients and 1 334 controls.Bioinformatics tools were employed to evaluate the consequences of identified variants.Result：Three variants（c.494C〉T,c.316＋36G〉A and c.423-7G〉C）were identified in the 60 thrombophilic patients.Their minor allele frequencies are all higher than 0.1and they were predicted to be benign or tolerated.In contrast,the affected amino acid in p.Arg596 Leu and p.Arg596 Gln reported previously were highly conserved among various species.However,the two mutations were not observed in the study population.Conclusion：p.Arg596 Leu and p.Arg596 Gln may be very rare and antithrombin resistance is not a common risk factor for inherited thrombophilia in central China.
出处
《临床血液学杂志》
CAS
2016年第1期16-19,共4页
Journal of Clinical Hematology
基金
国家自然科学基金(No:81370622
No:81400099)
关键词
抗凝血酶抵抗
易栓症
静脉血栓栓塞症
凝血酶原
antithrombin resistance
thrombophilia
venous thromboembolism
prothrombin
