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

Wong, WMR; Stephens, JW; Acharya, J; Hurel, SJ; Humphries, SE; Talmud, PJ; (2004) The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease. Journal of Lipid Research , 45 (8) pp. 1565-1571. 10.1194/jlr.M400130-JLR200. Green open access

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Abstract

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.

Type: Article
Title: The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1194/jlr.M400130-JLR200
Publisher version: https://doi.org/10.1194/jlr.M400130-JLR200
Language: English
Additional information: Copyright © 2004 by the This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.American Society for Biochemistry and Molecular Biology, Inc.
Keywords: apolipoprotein A-IV, association study, oxidized low density lipoprotein, total antioxidant status
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10145606
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