Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies

Aki S. Havulinna,Christian Ehnholm,Josefin Ahnström,Olof Axler,Björn Dahlbäck,Ruth Frikke-Schmidt,Veikko Salomaa,Matti Jauhiainen,Anne Tybjærg-Hansen

doi:10.1194/jlr.m700471-jlr200

Abstract

Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-beta-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74-1.27) and 0.92 (0.84-1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study.

Highlights

Apolipoprotein M, a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL
To be able to expand Apolipoprotein M (apoM) research to larger human clinical contexts, we have developed a specific quantitative sandwich ELISA for the measurement of apoM in human plasma and serum [10]
ApoM levels and other clinical and laboratory data were available on 921 cases and 944 controls

Summary

Introduction

Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). There was no significant difference in mean apoM level between CHD and control subjects in either study. Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies. Large epidemiological studies have established an association between an increased risk for CHD and low levels of HDL-cholesterol [2, 3]. A noteworthy feature of apoM is the lack of a signal peptidase cleavage site in the apoM amino acid sequence, explaining why circulating apoM retains its signal peptide [8] This unusual property of an extracellular protein is shared with two other HDL-associated proteins, namely paraoxonase-1.

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