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Qualitative and quantitative effects of APOE genetic variation on plasma C-reactive protein, LDL-cholesterol, and apoE protein

Genes & Immunity volume 7, pages 211–219 (2006)Cite this article

Abstract

A genetic link between lipid metabolism and inflammation has been suggested by the association between variation in the APOE gene and plasma C-reactive protein (CRP). This association was confirmed among Caucasians and extended to an African-American population, and the well-known associations of APOE variation with LDL-C and apoE protein were also observed. While eight common variants in APOE were examined, the association with CRP involved primarily the two nonsynonymous SNPs that define the major ɛ2, ɛ3, and ɛ4 alleles. In particular, the strongest link involved lower CRP levels among carriers of the APOE ɛ4 allele that also contributes to the risk of cardiovascular and Alzheimer's diseases as well as to higher lipid levels. A lesser effect was characterized by lower CRP levels among carriers of a subtype of the ɛ3 allele. The magnitude of the association with plasma CRP was at least as great as the effect of variation in the CRP gene itself. Quantitative analysis suggested that the effect on CRP is more likely a consequence of intrinsic functional differences among the E2, E3, and E4 apoE proteins than different levels of apoE protein or LDL-C in the plasma.

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Abbreviations

ANOVA:

analysis of variance

ApoA:

apolipoprotein A

ApoB:

apolipoprotein B

ApoE:

apolipoprotein E

BMI:

body mass index

CRP:

C-reactive protein

CVD:

cardiovascular disease

ELISA:

enzyme-linked immunosorbent assay

HDL-C:

high density lipoprotein cholesterol

HRT:

hormone replacement therapy

LDL-C:

low-density lipoprotein cholesterol

PHS:

Physicians’ Health Study

SNP:

single nucleotide polymorphism

WHS:

Women's Health Study

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Acknowledgements

We thank Lynda Rose for contributions to the statistical analysis, Gary Bradwin for biomarker determinations, and Peter Libby for helpful suggestions. This work was supported by Grants from the Donald W Reynolds Foundation (Las Vegas, NV) and the Fondation Leducq (Paris, France).

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Authors and Affiliations

  1. Division of Preventive Medicine and Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA

    D I Chasman, R Y Zee & P M Ridker

  2. Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA

    P Kozlowski & D J Kwiatkowski

  3. Donald W Reynolds Cardiovascular Clinical Research Center on Atherosclerosis at Harvard Medical School, Boston, MA, USA

    D I Chasman, P Kozlowski, R Y Zee, D J Kwiatkowski & P M Ridker

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  1. D I Chasman
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Correspondence to D I Chasman.

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Chasman, D., Kozlowski, P., Zee, R. et al. Qualitative and quantitative effects of APOE genetic variation on plasma C-reactive protein, LDL-cholesterol, and apoE protein. Genes Immun 7, 211–219 (2006). https://doi.org/10.1038/sj.gene.6364289

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