全外显子测序在高原地区静脉血栓患者中筛查致病突变的应用

Screening for Pathogenic Variants in High Altitude Venous Thromboembolism Cohort Using Whole-Exome Sequencing

目的利用全外显子测序技术筛查高原静脉血栓栓塞人群中的基因突变情况。方法选取2022年12月至2023年12月在阿坝藏族羌族自治州人民医院就诊的静脉血栓栓塞症患者35例。采集研究对象的外周血,提取全基因组DNA进行全外显子测序,应用生物信息学方法筛选共有突变基因、候选基因,并进行致病性判断。结果35例患者中,筛选出共有突变基因2312个,优先级分类H*中筛选出50个基因变异。优先级分类H+中筛选出20个基因变异,与疾病直接相关候选基因26个,与候选基因相关的基因1757个,致病基因7个,可能致病基因21个,致病性不明确基因1605个,发现东亚人群新发变异基因25个。结论本研究中筛选的易感基因突变与深静脉血栓发病密切,在东亚人群中普遍存在,但在地理分布上存在一定差异,相关基因未来可作为潜在生物标记和治疗靶点。

Objective To screen for gene mutations in high altitude venous thromboembolism(VTE)people using whole-exome sequencing(WES).Methods A total of 35 patients with VTE treated in People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture from December 2022 to December 2023 were selected.The peripheral blood samples of the research subjects were collected,and whole genome DNA was extracted for WES.Bioinformatic methods were applied to screen for the common mutant genes.And based on the results of common mutant genes,the candidate genes were screened out for pathogenicity identification.Results A total of 2312 gene variants were screened out in 35 patients,among which 50 gene variants were screened out in priority classification H*.A total of 20 gene variants were identified by priority classification H+.And 26 seed genes directly related to VTE and 1757 predicted genes related to the seed genes were screened out,including 7 pathogenic genes,21 predicted genes and 1605 genes with unclear pathogenicity.And 25 new mutations were found in East Asian population.Conclusion The susceptibility gene mutations screened out in this study are closely associated with VTE,which are common in East Asian populations,but vary in geographical distribution.The related genes could be used as potential biomarkers and therapeutic targets in the future.