Deep vein thrombosis (DVT) is the blood clot formed in a vein deep in body, mostly occurred in the lower leg or thigh. Early studies indicate that DVT is a complex disorder affected by both environmental and genetic factors. Previous biological evidence have indicated that KEAP1 gene may play an important role in the pathogenesis of DVT. In the present study, we aimed to investigate the genetic association between genetic polymorphisms of KEAP1 gene and the risk of DVT in Han Chinese population. A total of 2558 study subjects comprised of 660 DVT following orthopedics surgery cases and 1898 controls were recruited as discovery sample. In addition, we have also recruited another independent sample sets including 704 DVT following orthopedics surgery cases and 1056 controls for replication. Ten tag SNPs located on KEAP1 gene were selected for genotyping. Single marker based association analyses were conducted at both allelic and genotypic levels. SNPs that passed the Bonferroni correction in the discovery stage were genotyped in the replication dataset. Bioinformatics tools including PolymiRTS, GTEx, STRING and Gene Ontology database were utilized to investigate the functional consequences of the significant SNPs. SNP rs3177696 was identified to be significantly associated with risk of DVT in the study subjects. The G allele of SNP rs3177696 was significantly related to decreased risk of DVT. Functional consequences of SNP rs3177696 were obtained based on bioinformatics analyses. The G allele of SNP rs3177696 was related to the increased gene expression level of KEAP1. In summary, we have identified KEAP1 gene to be a potential susceptible locus for DVT in Han Chinese population. Further bioinformatics analyses have provided supportive evidence for the functional consequence of the significant SNP.
Keywords: Case–control study; Deep vein thrombosis; KEAP1; Single nucleotide polymorphisms.