Skip to Main content Skip to Navigation
Journal articles

Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk

Abstract : Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06–10.64] (p = 1.73 10−14). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10−6, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.
Document type :
Journal articles
Complete list of metadata

Cited literature [20 references]  Display  Hide  Download
Contributor : Gestionnaire Hal-Upmc Connect in order to contact the contributor
Submitted on : Wednesday, May 3, 2017 - 10:02:45 AM
Last modification on : Friday, December 3, 2021 - 12:13:11 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License



P. Suchon, Marie Germain, A. Delluc, D. Smadja, X. Jouven, et al.. Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk. Scientific Reports, Nature Publishing Group, 2017, 7, pp.45507. ⟨10.1038/srep45507⟩. ⟨hal-01517355⟩



Record views


Files downloads