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European Heart Journal Advance Access originally published online on March 26, 2009
European Heart Journal 2009 30(10):1263-1269; doi:10.1093/eurheartj/ehp090
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Association between the adiponectin promoter rs266729 gene variant and oxidative stress in patients with diabetes mellitus

Sarah L. Prior1, David R. Gable2, Jackie A. Cooper2, Stephen C. Bain1, Steven J. Hurel3, Steve E. Humphries2 and Jeffrey W. Stephens1,*

1 Diabetes Research Group, Institute of Life Sciences, Swansea University, Singleton Park, Swansea, Wales SA2 8PP, UK
2 Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF, UK
3 Department of Diabetes and Endocrinology, UCL Hospitals, London W1T 3AA, UK

Received 20 August 2008; revised 15 February 2009; accepted 18 February 2009; online publish-ahead-of-print 26 March 2009.

* Corresponding author. Tel: +44 1792 704078, Fax: +44 1792 703214, Email: j.w.stephens{at}swansea.ac.uk

Aims: Low levels of adiponectin are associated with type 2 diabetes and coronary heart disease (CHD). Recent evidence also suggests that low levels of adiponectin are associated with increased oxidative stress. Our aim was to examine the association between the rs266729 promoter gene variant (–11377C > G) and plasma markers of oxidative stress in diabetes subjects.

Methods and results: Seven hundred and sixty-seven Caucasian subjects with diabetes were successfully genotyped (CC/CG/GG). Genotype data were analysed in relation to plasma total antioxidant status (TAOS) and Oxidized-LDL (Ox-LDL). Plasma adiponectin measurements were available in 206 samples. There was a significant association between genotype and plasma TAOS (CC: 42.1 ± 13.4% vs. CG: 42.0 ± 12.0% vs. GG: 47.9 ± 12.0%, P = 0.02; for CC/CG vs. GG, P = 0.006). With respect to Ox-LDL, CC subjects had 8% higher plasma Ox-LDL compared with CG/GG [CC vs. CG vs. GG: 48.5 (36.3–60.2) U/L vs. 44.8 (35.6–54.1) U/L vs. 44.9 (41.2–49.1) U/L, for CC vs. CG/GG P = 0.03]. For plasma adiponectin, GG subjects had the highest levels [CC vs. CG vs. GG: 8.18 (5.69–15.38) µg/mL vs. 7.12 (5.34–12.97) µg/mL vs. 11.84 (6.98–25.25) µg/mL, P = 0.09; for CC/CG vs. GG, P = 0.05].

Conclusion: This study shows an association between a promoter variant in the adiponectin gene and plasma markers of oxidative stress. In line with previous studies, this work supports an antioxidant role for adiponectin which may explain its cardioprotective effect. Further prospective study is necessary to explore the effect of this gene variant in diabetes in relation to CHD risk and oxidative stress.

Key Words: Adiponectin • Oxidative stress • rs266729 • Gene • Coronary heart disease • Diabetes


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