Identification of new regulatory mechanisms that determine coagulation FXI plasma concentration

Abstract

FXI is a protein in the coagulation cascade in humans proven to be involved in the propagation and stabilization of developing thrombi in previous studies. The regulatory mechanisms for FXI are not well understood. Therefore an investigation to find regulatory mechanisms for FXI was performed. A meta-analysis was conducted, consisting of six Genome-wide association studies in which the trait was FXI levels in plasma. Three genome wide significant loci were found that also were significant in a replication study, in which three cohorts not included in the discovery set were used. Functional annotation, pathway analysis and eQTL analysis of these three loci yielded three genes believed potentially responsible for the regulation of FXI. Two of these three genes were chosen for a microRNA binding prediction search. Several microRNAs were found, and one was analyzed with a luciferase reporter assa