Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Mar;70(3):567-74.
doi: 10.1086/339259. Epub 2002 Jan 22.

A quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease

José Manuel Soria  1 , Laura Almasy, Juan Carlos Souto, Delphine Bacq, Alfonso Buil, Alexandra Faure, Elisabeth Martínez-Marchán, José Mateo, Montserrat Borrell, William Stone, Mark Lathrop, Jordi Fontcuberta, John Blangero
Affiliations

A quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease

José Manuel Soria et al. Am J Hum Genet. 2002 Mar.

Abstract

One approach to the identification of genetic loci that influence complex diseases is through the study of quantitative risk factors correlated with disease susceptibility. Factor XII (FXII) plasma levels, a related phenotype correlated with thrombosis, is such a risk factor. We conducted the first genomewide linkage screen to localize genes that influence variation in FXII levels. Two loci were detected: one on chromosome 5 and another on chromosome 10 (LOD scores 4.73 and 3.53, respectively). On chromosome 5, the peak LOD score occurred in the 5q33-5ter region, near the FXII gene. Addition of a 46C/T mutation in the FXII gene increased the multipoint LOD score to 10.21 (P=3.6 x 10(-12)). A bivariate linkage analysis of FXII activity and thrombosis further improved the linkage signal (LOD = 11.73) and provided strong evidence that this quantitative-trait locus (QTL) has a pleiotropic effect on the risk of thrombosis (P=.004). Linkage analysis conditional on 46C/T indicated that this mutation alone cannot explain the chromosome 5 signal, implying that other functional sites must exist. These results represent the first direct genetic evidence that a QTL in or near the FXII gene influences both FXII activity and susceptibility to thrombosis and suggest the presence of one or more still unknown functional variants in FXII.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Results of the initial linkage screen
Figure 2
Figure 2
Initial and conditional LOD scores on chromosome 10
Figure 3
Figure 3
Detailed linkage results for chromosome 5
Figure 4
Figure 4
Detailed linkage results for chromosome 5 when the 46C/T variant was added
See this image and copyright information in PMC

References

Electronic-Database Information

    1. ABI-Prism, http://www.appliedbiosystems.com/ (for genetic markers)
    1. Centre National de Genotypage, http://www.cng.fr/ (for genetic markers)
    1. Genome Database, http://www.gdb.org (for genetic markers)
    1. Center for Medical Genetics, Marshfield Medical Research Foundation http://research.marshfieldclinic.org/genetics/ (for genetic markers)
    1. Southwest Foundation for Biomedical Research, http://www.sfbr.org/ (for SOLAR program package)

References

    1. Allison DB, Neale MC, Zannolli R, Schork NJ, Amos CI, Blangero J (1999) Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci–mapping procedure. Am J Hum Genet 65:531–544 - PMC - PubMed
    1. Almasy L, Blangero JC (1998) Multipoint quantitative trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211 - PMC - PubMed
    1. Amos CI (1994) Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet 54:535–543 - PMC - PubMed
    1. Anderson FA, Wheeler HB, Goldberg RJ, Hosmer DW, Forcier A, Patwardhan NA (1991) A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 151:933–938 - PubMed
    1. Blangero J, Williams JT, Almasy L (2000) Robust LOD scores for variance component-based linkage analysis. Genet Epidemiol Suppl 19:S8–S14 - PubMed

Publication types

LinkOut - more resources