Whole Exome Sequencing Identifies genetic variants in Chinese Han
pregnant women with Venous thromboembolism-a case control study
Abstract
Objective Venous thromboembolism (VTE) is a common health problem. This
study aimed to identify genetic variants associated with pregnancies
with VTE. Design A case-control experimental study. Setting Ten
hospitals in Shanghai. Sample Blood samples from 25 pregnant patients
with VTE and 17 pregnant controls without VTE. Methods All samples were
sequenced by whole exome sequencing (WES). Functional and enrichment
analyses and PPI network were performed using DAVID and STRING database.
Primary outcome P-value and OR were obtained by Pearson’s chi-squared
test and logistic regression. Results 5810 significant variants
annotated in 3417 genes, were associated with pregnancies with VTE (P
< 0.05). Fifty-six variants annotated in 46 genes (P
< 0.001) were identified. Logistic analysis revealed that
rs7099478 in GRK5, rs8041208 in WDR72, rs17215792, rs13035688, rs6725221
and rs3214417 in KLF7 were associated with an increased risk of
developing VTE (P < 0.05, OR > 1). In addition,
Pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA
replication were associated with VTE in pregnancies. Conclusions Several
variants in KLF7, GRK5, and WDR72 may be genetic risk factors for VTE in
pregnancies. CDC7 and MCM6 may be related to the pathogenic process of
VTE in pregnancies. Notably, the KLF7 gene with 4 genetic variants was
found to be associated with lipid metabolism and cardiovascular
diseases. Funding The National Natural Science Foundation of China
(No.81472990) and Clinical Research Project of Shanghai Municipal
Commission of Health and Family Planning (No.201840095) Keywords
Pregnant, Venous thromboembolism, whole exome sequencing, KLF7