Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus

Jones, D.A.; Prior, S.L.; Tang, T.S.; Bain, S.C.; Hurel, S.J.; Humphries, S.E.; Stephens, J.W.

doi:10.1016/j.diabres.2010.07.009

« Previous Next »Diabetes Research and Clinical Practice
Volume 90, Issue 2 , Pages 196-201, November 2010

Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus

D.A. Jones
- Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK
- Corresponding author. Tel.: +44 0 1792 295073; fax: +44 0 1792 602147.
S.L. Prior
- Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK
T.S. Tang
- Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK
S.C. Bain
- Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK
S.J. Hurel
- Department of Diabetes & Endocrinology, UCL Hospitals, London W1T 3AA, UK
S.E. Humphries
- Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, London WC1E 6JF, UK
J.W. Stephens
- Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK

Received 21 April 2010; received in revised form 19 July 2010; accepted 22 July 2010. published online 23 August 2010.

Abstract

Mitochondrial superoxide dismutase 2 (SOD2) is an endogenous anti-oxidant enzyme. The rs4880 gene variant results in a C>T substitution, influencing SOD enzymatic activity. This variant has been associated with micro- and macro-vascular complications in diabetes mellitus. Our aim was to examine the association between this variant and coronary heart disease (CHD) risk in a cross-sectional sample of subjects with diabetes.

776 Caucasian subjects with diabetes were genotyped. CHD risk, oxidised-LDL and plasma total anti-oxidant status (TAOS) were analysed in relation to genotype. In females, the TT genotype was associated with CHD (CC/CT/TT: No CHD vs. CHD: 22.4/56.0/21.6% vs. 12.0/50.0/38.0%, p=0.03; for CC/CT vs. TT, p=0.01). The odds ratio for CHD associated with the TT genotype compared to CC/CT was 2.22 [95%CI: 1.17–4.24], p=0.01. The TT genotype was also associated with significantly lower plasma TAOS. In males, no association was observed between genotype and CHD risk, but CHD was significantly associated with age, lower HDL, higher triglycerides, higher BMI and cigarette smoking.

The TT genotype of this variant is associated with increased CHD risk and lower plasma anti-oxidant defences in females with diabetes. This modest genotype-effect is not apparent in males where traditional risk factors may play a greater role.

Keywords: Superoxide dismutase, Gene variant, Oxidative stress, Diabetes, CHD, rs4880, Mitochondria, Total anti-oxidant status