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- Title
Genome wide association study for plasma levels of natural anticoagulant inhibitors and protein C anticoagulant pathway: the MARTHA project.
- Authors
Oudot-Mellakh, Tiphaine; Cohen, William; Germain, Marine; Saut, Noémie; Kallel, Choumous; Zelenika, Diana; Lathrop, Mark; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel
- Abstract
Summary Deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) or an impaired PC anticoagulant pathway increase the risk of venous thrombosis (VT). By conducting a genome-wide association study (GWAS) on two independent samples of VT patients totalling 951 subjects typed for 472 173 single nucleotide polymorphisms (SNPs), we observed that common SNPs explain 21% and 27% of the genetic variance of plasma AT and PS levels, even though no SNP reached genome-wide significance. For PC, we showed that two PROCR SNPs, rs867186 (Ser219Gly) and rs6060278, additionally explained c. 20% ( P = 1·19 × 10−31) of the variance of plasma PC levels. We also observed that c. 40% of the remaining genetic variance of PC levels could be due to yet unidentified common SNPs. The PROCR locus was also found to explain c. 8% ( P < 10−10) of agkistrodon contortrix venom (ACV) (exploring the PC pathway) variability which was under the main control of the F5 and F2 loci that further explained about 40% and 10%, respectively. We presented here the first GWAS for plasma AT and free-PS levels and ACV in Caucasian samples. We identified three independent loci associated with ACV ( F2, F5 and PROCR) and replicated two independent effects on plasma PC levels at the PROCR locus.
- Subjects
GENOMES; ANTICOAGULANTS; PROTEIN C; ANTITHROMBINS; PROTEIN S; VENOUS thrombosis; GENETIC polymorphisms; LOCUS (Genetics)
- Publication
British Journal of Haematology, 2012, Vol 157, Issue 2, p230
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2011.09025.x