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Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships

Journal of Human Hypertension volume 22, pages 102–110 (2008)Cite this article

Abstract

We carried out univariate and bivariate linkage analyses to identify genomic regions that may influence plasma levels of C-reactive protein (CRP) and fibrinogen and exert pleiotropic effects on both traits. Subjects included African American (AA, n=1310, mean age 62.7±9.4 years) and non-Hispanic white (NHW, n=796, mean age 58.4±9.8 years) belonging to hypertensive sibships. Plasma CRP was measured by an immunoturbidimetric assay and fibrinogen by the Clauss method. Genotyping was performed at 366 microsatellite marker loci spaced ∼10 cM apart across the 22 autosomes. Estimation of heritability and linkage analyses was carried out using a variance components approach. Significant heritability was noted for CRP (0.38 in AA and 0.37 in NHW subjects) and fibrinogen (0.44 in AA and 0.28 in NHW subjects). Significant genetic correlation between CRP and fibrinogen was present in both AA (0.39) and NHW (0.40) subjects. In univariate linkage analysis, the maximum logarithm of odds (LOD) score for CRP was on chromosome 10q22 in NHW (LOD=1.69, 106.75 cM, P=0.0026) and for fibrinogen on chromosome 2 in AA (LOD=2.14, 55.5 cM, P=0.0009) subjects. Bivariate linkage analysis demonstrated suggestive evidence of linkage (defined as LOD score⩾2.87) for both traits on chromosome 12 (LOD=3.44, 152.16 cM, P=0.0003) in AA and on chromosome 21 (LOD=3.03, 13.05 cM, P=0.0008) in NHW subjects. Plasma CRP and fibrinogen levels are heritable and genetically correlated. Linkage analyses identified several chromosomal regions that may harbour genes influencing CRP and fibrinogen levels and exert pleiotropic effects on both traits.

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Acknowledgements

This work was supported by grants HL75794, HL 71917, U01 HL 54457, UO1 HL 54464 and the General Clinical Research Center Grant M01 RR00585 from the National Institutes of Health.

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  1. K Ding and D Feng: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

    K Ding, D Feng & I J Kullo

  2. Department of Biostatistics, Mayo Clinic, Rochester, MN, USA

    M de Andrade

  3. Department of Medicine, University of Mississippi, Jackson, MS, USA

    T H Mosley Jr

  4. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    S T Turner

  5. Human Genetics Center and Institute of Molecular Medicine, University of Texas–Houston Health Science Center, Houston, TX, USA

    E Boerwinkle

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  1. K Ding
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Correspondence to I J Kullo.

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Ding, K., Feng, D., de Andrade, M. et al. Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships. J Hum Hypertens 22, 102–110 (2008). https://doi.org/10.1038/sj.jhh.1002297

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