English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

SummaryEssentials    Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited.  We performed a genome‐wide analysis of variants influencing FSAP activity in Scandinavian cohorts.  We replicated an association for Marburg‐1 and identified an association for a  HABP2  stop variant.  We identified a novel locus near  ADCY2  as a potential additional regulator of FSAP activity.Summary   Background  Factor  VII ‐activating protease ( FSAP ) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma  FSAP  activity is highly variable among healthy individuals and, apart from the low‐frequency missense variant Marburg‐I (rs7080536) in the  FSAP ‐encoding gene   HABP 2 , determinants of this variation are unclear.    Objectives  To identify novel genetic variants within and outside of the   HABP 2  locus that influence circulating  FSAP  activity.    Patients/Methods  We performed an exploratory genome‐wide association study ( GWAS ) on plasma  FSAP  activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene‐based tests. Using  GWAS , we confirmed the strong association between the Marburg‐I variant and  FSAP  activity.   HABP 2  was also significant in the gene‐based analysis, and remained significant after exclusion of Marburg‐I carriers. This was attributable to a rare   HABP 2  stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in  FSAP  activity as Marburg‐I carriers, and this finding was replicated. A secondary genome‐wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of   ADCY 2 , which encodes a protein catalyzing the formation of  cAMP .    Results and Conclusions  This study verified the Marburg‐I variant to be a strong regulator of  FSAP  activity, and identified an   HABP 2  stop variant with a similar impact on  FSAP  activity. A novel locus near   ADCY 2  was identified as a potential additional regulator of  FSAP  activity.

Genome‐wide analysis of genetic determinants of circulating factor VII ‐activating protease ( FSAP ) activity