Loss of function in protein Z (PROZ) is associated with increased risk of ischemic stroke in the UK Biobank.

ABSTRACT:

Background

The vitamin K-dependent coagulation factor protein Z (PZ), encoded by the PROZ gene, is canonically considered to have anticoagulant effects through negative regulation of factor Xa. Paradoxically, higher circulating PZ concentrations have repeatedly been associated with an elevated risk of acute ischemic stroke.

Objectives

We performed a large-scale genetic association study to examine the relationship between germline genetic variants in PROZ and the risk of ischemic stroke.

Methods

Using whole-exome sequencing and clinical data for 416 711 participants in the UK Biobank (UKB), we identified individuals with rare (minor allele frequency ≤0.1%) putatively function-altering variants in PROZ. Using Firth's logistic regression and controlling for known stroke

SUBMITTER: Haj AK 

PROVIDER: S-EPMC11725435 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature