Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Premature coronary artery disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, this is not explained by traditional cardiovascular risk factors or markers of inflammation. Little is known about the contribution of genetic variation to atherosclerosis in this patient population. Therefore, we examined the hypothesis that, in patients with SLE, candidate gene polymorphisms were associated with the presence of coronary atherosclerosis.
Methods: One hundred and twenty five patients with SLE, enrolled in an ongoing study to evaluate the prevalence and associated risk factors of coronary atherosclerosis in SLE, were studied. Patients fulfilled the 1997 American College of Rheumatology classification criteria for SLE and were 18 years or older. Coronary artery calcium (CAC), a non-invasive measurement of coronary atherosclerosis, was measured by electron beam computed tomography. Using the Illumina Goldengate platform, we determined the genotype of 714 single-nucleotide polymorphisms (SNPs) in 176 selected candidate genes. Candidate genes were selected because of their relevance to autoimmune or cardiovascular risk. The associations between the presence of CAC and individual SNPs were assessed with logistic regression, adjusted for age, gender, and race. To account for multiple comparisons, a false discovery rate (FDR) threshold of 20% was specified.
Results: Patients with SLE were 41±12 years old, 91% were women and 64% were Caucasian. The presence of CAC was detected in 33 patients (26%). After adjustment for age, race, and sex, associations were detected for CSF1, ADIPOQ, REST, VCAM1, MIF, TNFSF4, INS, IRF5, TH and HMOX1 (Table). However, none of these associations remained significant after FDR correction.
Table: Genetic Association with Coronary Atherosclerosis in Patients with SLE
|
SNP |
Gene |
Major, minor allele |
Minor allele frequency |
Odds ratio* (95% CI) |
p-value |
|
rs333947 |
CSF1 |
G,A |
0.18 |
4.71 (1.93-11.53) |
0.001 |
|
rs7649121 |
ADIPOQ |
A,T |
0.20 |
0.05 (0.01-0.30) |
0.001 |
|
rs1862513 |
REST |
C,G |
0.31 |
2.94 (1.47-5.93) |
0.002 |
|
rs3917009 |
VCAM1 |
C,T |
0.07 |
3.75 (1.53-9.22) |
0.004 |
|
rs875643 |
MIF |
G,A |
0.41 |
0.36 (0.17-0.74) |
0.005 |
|
rs333970 |
CSF1 |
C,A |
0.45 |
0.39 (0.20-0.77) |
0.006 |
|
rs738806 |
MIF |
A,G |
0.25 |
3.24 (1.41-7.45) |
0.006 |
|
rs34124816 |
REST |
A,C |
0.06 |
6.69 (1.51-29.72) |
0.012 |
|
rs3850641 |
TNFSF4 |
A,G |
0.14 |
3.15 (1.28-7.78) |
0.013 |
|
rs3842748 |
INS |
C,G |
0.29 |
0.35 (0.15-0.80) |
0.013 |
|
rs3745369 |
REST |
G,C |
0.41 |
2.49 (1.20-5.15) |
0.014 |
|
rs1874328 |
IRF5 |
A,G |
0.39 |
0.38 (0.17-0.83) |
0.015 |
|
rs2070762 |
TH |
A,G |
0.44 |
2.43 (1.18-4.98) |
0.015 |
|
rs333968 |
CSF1 |
C,T |
0.26 |
0.41 (0.19-0.88) |
0.022 |
|
rs11912889 |
HMOX1 |
G,A |
0.15 |
0.32 (0.12-0.85) |
0.022 |
|
rs3093037 |
CSF1 |
C,T |
0.10 |
0.21 (0.06-0.81) |
0.024 |
* Odds ratios for the comparison between minor and major allele.
Conclusion: Our results suggest that polymorphisms of genes coding CSF-1, adiponectin, resistin, VCAM-1, MIF, TNFSF-4, insulin, IRF-5, TH, and HMOX-1 may be associated with the presence of coronary atherosclerosis in patients with SLE. Studies in additional cohorts will be informative.
Disclosure:
C. P. Chung,
None;
J. F. Solus,
None;
A. Oeser,
None;
C. Li,
None;
P. Raggi,
None;
J. R. Smith,
None;
C. M. Stein,
None.
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