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Journal of Lipid Research, Vol. 45, 1565-1571, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

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

Wai-man R. Wong^1,*, Jeffrey W. Stephens^1,*,, Jayshree Acharya^*, Steven J. Hurel, Steve E. Humphries^* and Philippa J. Talmud^2,*

^* Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF, United Kingdom
Department of Diabetes and Endocrinology, University College London Hospitals, London W1T 3AA, United Kingdom

² To whom correspondence should be addressed. e-mail: p.talmud{at}ucl.ac.uk

Apolipoprotein A-IV (apoA-IV) has been postulated to be antiatherogenic. Transgenic APOA4/Apoe^–/– mice are protected against atherosclerosis, with plasma apoA-IV displaying antioxidant activity in vitro. In humans, there is an inverse relationship between apoA-IV levels and risk of coronary heart disease (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 with the rest (P = 0.04). Overall, there was no association between genotype and TAOS. However, in patients with CVD, homozygotes for the S347 allele had significantly lower TAOS compared with TT and TS subjects (31.2 ± 9.89% and 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 antioxidant capacity of apoA-IV, thus providing some explanation for the antiatherogenic role of apoA-IV and the higher CVD risk in S347 homozygotes.

Supplementary key words apolipoprotein A-IV • association study • oxidized low density lipoprotein • total antioxidant status

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