Biochemical and genetic risk factors for atherosclerosis in systemic lupus erythematosus

ABSTRACT

Systemic lupus erythematosus [SLE] is associated with an increase in the risk of premature cardiovascular complications caused by accelerated atherosclerosis which significantly contributes to morbidity and mortality. Carotid ultrasonography is a very sensitive imaging tool to detect premature atherosclerosis and measurements of carotid intima-media thickness [IMT] assess the extent and the severity of systemic atherosclerosis. The pathogenesis of accelerated atherosclerosis in SLE is not clear; inflammation and endothelial dysfunction in addition to genetic risk factors represent important factors in the onset of atherosclerosis. To evaluate the relation between asymmetric dimethylarginine [ADMA], high sensitive C-reactive protein [hs-CRP], monocyte chemoattractant protein-1 [MCP-1] [both serum levels and the genotypes of the MCP-1 A-2518G polymorphism] with the development of carotid atherosclerosis in patients with SLE and their relation to disease activity. In the present study, 30 non-menopause SLE female patients and 20 healthy age-matched females were included. Both patients and controls were subjected to evaluation of body mass index [BMI], IMT, serum glucose, serum lipids, hs-CRP, ADMA, MCP-1 [both serum level and gene polymorphism]. Serum ADMA, hs-CRP, and MCP-1, levels were measured by enzyme-linked immunosorbent assay. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Values for IMT, hs-CRP, ADMA and MCP-1 were significantly higher in patients with SLE than in healthy controls with more significant increase in SLE patients with IMT >/=1 mm than in those with IMT <1 mm. Carotid IMT was significantly positively correlated with all the studied variables except for age, BMI and FBS, but significantly negatively correlated with HDL-C in all SLE patients. G/G genotype of MCP-1 A-2518G gene was more frequent in SLE patients than controls. IMT, hs-CRP, ADMA and MCP-1 from patients with G/G phenotypes were markedly higher than those from patients with the A/A genotype. In multiple regression analysis, ADMA and MCP-1 were the strongest independent determinants of IMT in SLE patients. Assessment of high levels of ADMA, hs-CRP, MCP-1, in addition to the MCP-1 A-2518G polymorphism may play a role in the pathogenesis of accelerated atherosclerosis in SLE patients and would be useful in identifying the risk of developing cardiovascular disease. Development of a novel therapy targeting ADMA and MCP-1 may have a potential role in preventing the progression of increased IMT in SLE patients