Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Genetic Risk Factors for Thrombosis in An Ethnically Diverse Systemic Lupus Erythematosus (SLE) Population
Kaiser1, R., Li2, Y., Chang2, M., Catanese2, J., Begovich3, A.B., Criswell1, L.A.
Thrombosis is a devastating SLE complication. Established risk factors such as antiphospholipid antibodies (aPL) do not completely explain this increased thrombosis risk. We investigated whether previously described and novel single nucleotide polymorphisms (SNPs) recently associated with risk for thrombosis in the general (non-SLE) Caucasian population help explain the increased risk of thrombosis in an ethnically diverse SLE population.
Subjects were enrolled in a large SLE cohort through diverse recruitment sources, completed an extensive questionnaire, and had thrombosis phenotypes well-characterized. We genotyped 1513 SLE subjects for established and novel SNPs recently suggested to be associated with deep venous thrombosis in the general Caucasian population. Each SNP was tested for association with thrombosis in bivariate analysis. Statistically significant results from bivariate analyses (p<=0.05) were evaluated in a logistic regression model that included aPL, disease duration, ever history of smoking, and medication treatment history as covariates. In sensitivity analyses, thrombosis subgroups were analyzed as distinct outcomes because certain SNPs have been shown to be risk factors specifically for arterial or venous thrombosis.
1380 SLE patients (91%) were female, 874 (58%) Caucasian, 232 (15%) Hispanic, 190 (13%) African American and 217 (14%) Asian American. Average age at SLE diagnosis was 33.3 ± 13.4 years and average disease duration was 8.96 ± 8.2 years. 587 subjects (40%) were ever-smokers, and 841 (53%) had a history of immunomodulator therapy (cytoxan, methotrexate, etc.). 357 (25%) subjects had a total of 499 thrombotic events. 444 (31%) subjects were positive for either anticardiolipin antibodies or the lupus anticoagulant. No SNPs deviated from Hardy Weinberg Equilibrium. Table 1 summarizes multivariate genetic association results for the outcomes of arterial and venous thromboses. No SNPs were significantly associated with the combined outcome of venous and/or arterial thrombosis.
Table 1. Results of Multivariate Analyses
This is the first study to assess these genetic risk factors for thrombosis in a large, ethnically diverse SLE population and may help to identify SLE subjects at higher risk for thrombosis. Although confirmation of these findings in independent study populations is needed, the magnitude of some of these associations implies the potential for substantial clinical significance.
To cite this abstract, please use the following information:
Kaiser, R., Li, Y., Chang, M., Catanese, J., Begovich, A.B., Criswell, L.A.; Genetic Risk Factors for Thrombosis in An Ethnically Diverse Systemic Lupus Erythematosus (SLE) Population [abstract]. Arthritis Rheum 2009;60 Suppl 10 :123