Document Detail

Genetic variants associated with protein C levels.
MedLine Citation:
PMID:  23387557     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Normal protein C (PC) plasma levels range widely in the general population. Factors influencing normal PC levels are thought to influence the risk of venous thrombosis. Little is known about the underlying genetic variants.
OBJECTIVES: We performed a genome scan of normal PC levels to identify genes that regulate normal PC levels.
PATIENTS/METHODS: We performed a variance components linkage analysis for normal PC levels in 275 individuals from a single, large family. We then sequenced candidate genes under the identified linkage peak in eight family members: four with high and four with low, but normal, PC levels. For variants showing a difference in carriers between those with high and low PC levels, we re-evaluated linkage in the 275 family members conditional on the measured genotype effect. Genotype-specific mean PC levels were determined using likelihood analysis. Findings were replicated in the Leiden Thrombophilia Study (LETS).
RESULTS: We identified a quantitative trait locus at chromosome 5q14.1 affecting normal PC plasma level variability. Next-generation sequencing of 113 candidate genes under the linkage peak revealed four SNPs in BHMT2, ACOT12, SSBP2 and XRCC4, which significantly increased PC levels in our thrombophilic family, but not in LETS.
CONCLUSIONS: We identified four genes at chromosome 5q14.1 that might influence normal PC levels. BHMT2 seems the most likely candidate to regulate PC levels via homocysteine, a competitive inhibitor to thrombin. Failure to replicate our findings in LETS might be due to differences between the studies in genetic background and linkage disequilibrium patterns.
C Y Vossen; B P Koeleman; S J Hasstedt; I J Nijman; I J Renkens; P W Callas; F R Rosendaal; E G Bovill
Related Documents :
24026677 - The familial dementia gene revisited: a missense mutation revealed by whole exome seque...
18285427 - A missense mutation in ptch2 underlies dominantly inherited nbccs in a chinese family.
16032697 - Prevalence of 9p21 deletions in uk melanoma families.
23542697 - Mutations in depdc5 cause familial focal epilepsy with variable foci.
9482577 - Population genetic diversity in relation to microsatellite heterogeneity.
24554057 - Gene-ethanol interactions underlying fetal alcohol spectrum disorders.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  11     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-09-30     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  715-23     Citation Subset:  IM    
Copyright Information:
© 2013 International Society on Thrombosis and Haemostasis.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Case-Control Studies
Genetic Linkage
Polymorphism, Single Nucleotide*
Protein C / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Protein C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Detection of early visual impairment in patients with epiretinal membrane.
Next Document:  The Accordion Antiretropulsive Device Improves Stone-Free Rates During Ureteroscopic Laser Lithotrip...