J. Lipid Res.
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A more recent version of this article appeared on August 1, 2004

Papers In Press, published online ahead of print June 1, 2004
J. Lipid Res., doi:10.1194/jlr.M400130-JLR200
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Submitted on April 5, 2004
Revised on May 7, 2004
Accepted on May 20, 2004

The APOA4 T347S variant is associated with reduced plasma total antioxidant status in subjects with diabetes mellitus and cardiovascular disease

Wai-man R. Wong, Jeffrey W. Stephens, Jayshree Acharya, Steven J. Hurel, Steve E. Humphries, and Philippa J. Talmud

Department of Medicine, University College London, London, London WC1E 6JF

Corresponding Author: p.talmud{at}ucl.ac.uk

Apolipoprotein (apo) A-IV has been postulated to be anti-atherogenic. Transgenic APOA4/Apoe-/- mice are protected against atherosclerosis, with plasma apoA-IV displaying anti-oxidant activity in vitro. In humans there is an inverse relationship between apoA-IV levels and risk of coronary heart dsease (CHD). Furthermore the APOA4 T347S rare allele has been associated with increased risk of CHD and reduced apoA-IV levels. Reduced total antioxidant status (TAOS) due to increased oxidative stress is implicated in the process of atherogenesis. Thus this study aimed to examine the association between the APOA4 T347S variant and TAOS in diabetic patients with (n=196) or without (n=509) cardiovascular disease (CVD). A higher percentage of CVD patients were present in the lowest quartile of TAOS, compared to the rest (p=0.04). Overall there was no association between genotype and TAOS, however in those with CVD, homozygotes for the S347 allele had significantly lower TAOS compared to TT and TS subjects (31.2% ± 9.89, 42.5%±13.04 TAOS respectively, p=0.0024) an effect that was not seen in the patients without CVD. This study offers direct support for an anti-oxidant capacity of apoA-IV, thus providing some explanation for the anti-atherogenic role of apoA-IV and the higher CVD risk in S347 homozygotes.


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