Exploring the pathogenesis of venous thromboembolism in pregnant women based on whole exome sequencing

LIU Bo; WANG Yun-ju; GAO Xia; LIU Meng-bin; SHANG Li

doi:10.13820/j.cnki.gdyx.20233575

Abstract：Objective To investigate the significance of whole exome sequencing(WES)in exploring the patho-genic genes of venous thromboembolism(VTE)in pregnant women.Methods From January 2019 to January 2022,pregnant women who underwent their first prenatal examination(between 16-24 weeks of gestation)at Shiyan People's Hospital were recruited and followed up to 42 days after delivery.A total of 12 pregnant women with VTE and 12 controls were included in the study.Blood samples were collected,and sequencing was performed using whole exome sequencing.Destructive variants identified in known thrombophilic genes and rare destructive variants potentially associated with preg-nancy-related VTE were discovered.Results WES detected a total of 360 827 changes in the VTE group.After filte-ring using the criteria of identifying rare pathogenic variants,the candidate variant list was reduced to 8 452,including 6756 variants of uncertain significance(VUS)and 14 potentially pathogenic variants.The samples contained 29 known thrombophilic variants,including 8 missense,3 nonsense,2 splice site deletions,1 protein-altering insertion and/or de-letion,5 frameshift mutations,7 synonymous mutations,and 3 intronic mutations.The top 5 genes with the highest muta-tion frequencies were coagulation factor V(F5,12.24％),followed by coagulation factor 2(F2,10.20％),PROS1(10.20％),PROC(8.16％),and SERPINA10(6.12％).Exon association studies showed that three exonic variants reached suggestive significance,namely TAS2R43(rs200893955,P=3.68 × 10-5),NRCAM(rs1269621,P=5.04 × 10-5,FDR=0.047 8),and ZFP41(rs6558339,P=8.85 × 10-5).Conclusion Pregnancy-related VTE may be pri-marily associated with the presence of known pathogenic variants,including F5,F2,and 14 potentially rare pathogenic va-riants.