Genetic variation and coronary atherosclerosis in patients with systemic lupus erythematosus.
Coronary artery disease is the major cause of mortality in patients with systemic lupus erythematosus (SLE). Increased cardiovascular risk in SLE is not explained by traditional risk factors. We examined the hypothesis that genetic variation contributes to the presence of coronary atherosclerosis in patients with SLE. The genotypes of single-nucleotide polymorphisms (SNP) in 152 candidate genes linked with autoimmune or cardiovascular risk were determined in 125 patients with SLE. Coronary artery calcium (CAC), a measure of coronary atherosclerosis, was detected in 32 patients (26%) by electron-beam computed tomography. Polymorphism in 20 of the candidate genes (ADAM33, ADIPOQ, CCL5, CCR7, CDKN2B, CSF1, IL4, IL12A, IL23R, INS, IRF5, MIF, MS4A1, PTGS1, PTPN22, RETN, SELE, TNFSF4, TNFRSF11B, and VCAM1) were nominally associated with the presence of CAC (p-values = 0.001-0.047 after adjustment for age, sex and race). Some of these are known susceptibility genes for SLE and others have been implicated in cardiovascular disease in other populations. No association withstood false discovery rate adjustment. Replication studies in additional cohorts of patients with SLE may be informative.
Departments of Medicine, Vanderbilt University, Nashville, TN, USA c.chung@vanderbilt.edu.
C P
CP
Chung
Departments of Medicine, Vanderbilt University, Nashville, TN, USA.
J F
JF
Solus
Departments of Medicine, Vanderbilt University, Nashville, TN, USA.
A
A
Oeser
Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
C
C
Li
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
P
P
Raggi
Departments of Medicine, Vanderbilt University, Nashville, TN, USA.
J R
JR
Smith
Departments of Medicine, Vanderbilt University, Nashville, TN, USA.
C M
CM
Stein
D000328:Adult; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
SNP; Systemic lupus erythematosus; atherosclerosis; genetic variation