论文部分内容阅读
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 newly discovered severe hereditary thrombophilia in the world, and its molecular basis is the function-enhanced mutation of the prothrombin gene. Such mutations are reported in three venous thromboembolism families in Japan (p. Arg 596 Leu) and Serbia (p. Arg 596 Gln), but it is unclear whether other regions of the world, including China, exist and are common. The purpose of this study was to investigate the existence of p.Arg596Leu, p.Arg596Gln and antithrombin resistance in our population with venous thromboembolism. Methods: Thrombospondin gene functional regions were sequenced in 60 patients with thrombophilia of unknown cause. The p.Arg596Leu and p.Arg596Gln mutations were performed in 1 304 and 1 334 case-control subjects using the restriction endonuclease HpaII Detection; the use of bioinformatics tools for p.Arg596Leu and p.Arg596Gln and other prothrombin genetic analysis of homology and possible hazards. Results: The genotypes of c.494C> T, c.316 + 36G> A and c.423-7G> C were detected in 60 patients with thrombophilia. The frequencies of minor alleles were all above 0.1, No functional changes; the contrary p.Arg596Leu and p.Arg596Gln predicted highly conserved in all species, but none of the two mutations were detected in all patients with venous thromboembolism. Conclusion: Our country p.Arg596Leu and p.Arg596Gln mutations may be extremely rare, hereditary anti-thrombin resistance is not a common factor in central China embolism.