Functional analysis of the genetic variability in the F7 gene promoter

Maria Sabater-Lleal, Miguel Chillón, Tom E. Howard, Estel Gil, Laura Almasy, John Blangero, Jordi Fontcuberta, José Manuel Soria

    Research output: Contribution to journalArticle

    20 Scopus citations

    Abstract

    The FVII level is considered a risk factor for cardiovascular disease. Some of the polymorphic differences in the promoter of the F7 gene have been associated with variations in FVII levels. However, linkage disequilibrium among those polymorphisms has made it difficult to pinpoint the true functional variants, so contradictory results have often appeared among various studies. We provide new findings of the effect of the polymorphisms in the promoter region of F7. In vitro transfection of 15 plasmids containing different combinations of F7 promoter polymorphisms was performed in HepG2 cells. We found that allelic variants -323ins10 and -122C strongly reduced promoter activity and that allelic variant -402A significantly increased promoter activity. We report the effect of a novel variant (-2989A) that significantly increases F7 expression levels. However, this novel allelic variant is in strong linkage disequilibrium with the -323ins10 variant in our Spanish population, which has a clear dominant effect over the -2989A variant and completely masks its effect. Our results have important implications for mapping genes affecting complex diseases using association studies. That is, they imply that true functional variants should be chosen to confirm the analyses and to ensure that the results can be reproduced in other populations. In addition, our results suggest that it would be informative to screen for the -2989A variant in other populations, since it may well be a risk factor for cardiovascular disease in populations where it does not appear with the decanucleotide insertion.

    Original languageEnglish (US)
    Pages (from-to)262-268
    Number of pages7
    JournalAtherosclerosis
    Volume195
    Issue number2
    DOIs
    StatePublished - Dec 1 2007

    Keywords

    • F7
    • FVII
    • Functional analyses
    • Promoter expression

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Fingerprint Dive into the research topics of 'Functional analysis of the genetic variability in the F7 gene promoter'. Together they form a unique fingerprint.

  • Cite this

    Sabater-Lleal, M., Chillón, M., Howard, T. E., Gil, E., Almasy, L., Blangero, J., Fontcuberta, J., & Soria, J. M. (2007). Functional analysis of the genetic variability in the F7 gene promoter. Atherosclerosis, 195(2), 262-268. https://doi.org/10.1016/j.atherosclerosis.2006.12.031