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Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis

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Abstract

Apolipoprotein B (apoB) is the sole protein component of low-density lipoprotein (LDL) and is thought to play an important role in atherogenesis. We performed a meta-analysis of the associations between the three most frequently investigated polymorphisms (XbaI, signal peptide insertion/deletion, EcoRI) in the apolipoprotein B (APOB) gene, lipid parameters, and the risk of ischemic heart disease (IHD). We restricted our analysis to Caucasians. Homozygotes for the XbaI X+ allele had significantly elevated levels of LDL cholesterol (LDL-C) and apoB, but a decreased risk (OR=0.80; 95%CI: 0.66–0.96) of IHD. Homozygosity for the signal peptide deletion allele was associated with similarly increased levels of LDL-C and apoB, and with an increased risk of IHD (OR=1.30; 95%CI: 1.08–1.58). Subjects homozygous for the rare EcoRI allele had significantly decreased levels of total and LDL cholesterol, but unaltered risk of IHD. We conclude that all three polymorphic apoB sites are associated with altered lipid levels, but not necessarily with a consistently altered risk of IHD. These data suggest that the relationship between apoB levels, hypercholesterolemia and IHD risk cannot have a simple molecular basis in the apoB gene.

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Acknowledgements

The authors gratefully acknowledge all authors who provided additional unpublished information regarding publications included in this review.

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Authors and Affiliations

  1. Department of Cardiology, Room F3-241, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    S. Matthijs Boekholdt & Ron J. G. Peters

  2. Department of Internal Medicine, University Hospital of Larissa, Larissa, Greece

    Katerina Fountoulaki

  3. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    John J. P. Kastelein

  4. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    Eric J. G. Sijbrands

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  1. S. Matthijs Boekholdt
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  2. Ron J. G. Peters
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Correspondence to S. Matthijs Boekholdt.

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Boekholdt, S.M., Peters, R.J.G., Fountoulaki, K. et al. Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis. Hum Genet 113, 417–425 (2003). https://doi.org/10.1007/s00439-003-0988-3

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