Protein C Levels Are Regulated by a Quantitative Trait Locus on Chromosome 16: Results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project

    loading  Checking for direct PDF access through Ovid



Protein C (PC) is a component of the protein C anticoagulant pathway. PC deficiency is a risk factor associated with venous thromboembolism. As part of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project, we conducted a genome-wide linkage scan to localize genes that influence variation in PC plasma levels.

Methods and Results—

PC levels were measured in 398 individuals belonging to 21 Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1-cM genetic map. Variance component linkage methods were used to evaluate linkage and to detect quantitative trait loci (QTL). A region on chromosome 16 (16q23), flanked by markers D16S3106 and D16S516, showed strong evidence of linkage with PC levels (LOD=3.69). This region contains 1 positional candidate gene, the NAD(P)H:dehydrogenase quinone 1 (NQO1), involved in vitamin K metabolism. The association of 1 SNP of this gene with PC levels (P =0.005) strongly supports the implication of NQO1 gene in the variability of PC levels.


These results illustrate the application of genomic scans to identify the genetic determinants of quantitative variation in a component of the hemostatic pathways. They provide strong evidence for a locus (QTL) on chromosome 16 that influences PC levels.

Related Topics

    loading  Loading Related Articles