Uncoupling Protein 2 as genetic risk factor for systemic lupus erythematosus: association with malondialdehyde levels and intima media thickness.

Background: Increased oxidative stress potentially leads to accelerated atherosclerosis and, consequently, cardiovascular diseases, the main cause of death in systemic lupus erythematous (SLE). To gain insight into these mechanisms, we studied the association of uncoupling protein (UCP) 2 genetic variants, gene involved in the mitochondrial production of reactive oxygen species, and oxidative stress with SLE and the presence of atherosclerosis.

Methods: Genetic analysis of the UCP2 -866G/A and UCP2 Ins/Del polymorphisms was performed in 45 SLE patients and 36 healthy controls by RFLP-PCR. Oxidation status was determined by measuring malondialdehyde (MDA) levels. Presence of subclinical atherosclerosis was investigated by evaluation of intima-media thickness using echo-color-Doppler carotid ultrasound examination.

Results: Allelic and genotypic frequencies of the SNPs analysed were evaluated by gene count. Significant association was found between UCP2-866A allele and susceptibility for SLE (P=0.001). Higher levels of MDA were found significantly increased in SLE patients (MDA, 5.05±3.36 µmol/L) compared to normal controls (MDA, 2.79±0.89 µmol/L) (P<0.0001).

Conclusions: Our results suggest that -866G/A UCP2 polymorphism is associated with SLE causing increased ROS production that, in turn, results in increased MDA levels responsible of accelerated atherosclerosis.