期刊
JOURNAL OF RHEUMATOLOGY
卷 39, 期 8, 页码 1603-1610出版社
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.111451
关键词
SYSTEMIC LUPUS ERYTHEMATOSUS; THROMBOSIS; POLYMORPHISM
类别
资金
- National Center for Research Resources, US Public Health Service [5 M01 RR-00079]
- Arthritis Foundation
- American College of Rheumatology Investigator Award
- Alliance for Lupus Research Target Identification in Lupus Award
- Kirkland Scholar Award
- UCSF Rosalind Russell Medical Research Center for Arthritis
- National Institutes of Health (NIH) [P60 AR053308, R01 AR44804, K24 AR02175]
- NIH [AR 43727]
- [K24 AR 002138]
- [P602 AR 30692]
- [P01 AR 49084]
- [UL 1 RR 025741]
- [P60 AR048095]
- [P01 AR049084]
- [5 UL1 RR025777]
Objective. Thrombosis is a serious complication of systemic lupus erythematosus (SLE). We investigated whether genetic variants implicated in thrombosis pathways are associated with thrombosis among 2 ethnically diverse SLE cohorts. Methods. Our discovery cohort consisted of 1698 patients with SLE enrolled in the University of California, San Francisco, Lupus Genetics Project and our replication cohort included 1361 patients with SLE enrolled in the PROFILE cohort. Patients fulfilled American College of Rheumatology SLE criteria, and data relevant to thrombosis were available. Thirty-three single nucleotide polymorphisms (SNP) previously shown to be associated with risk of deep venous thrombosis in the general population or implicated in thrombosis pathways were genotyped and tested for association with thrombosis in bivariate allelic analyses. SNP with p < 0.1 in the bivariate analyses were further tested in multivariable logistic regression models adjusted for age, sex, disease duration, antiphospholipid antibody status, smoking, nephritis, and medications. Results. In the discovery cohort, 23% of patients with SLE experienced a thrombotic event. SNP in the following genes demonstrated association with thrombosis risk overall in the discovery or replication cohorts and were assessed using metaanalytic methods: factor V Leiden (FVL) rs6025 (OR 1.85, p = 0.02) and methylenetetrahydrofolate reductase (MTHFR) rs1801133 (OR 0.75, p = 0.04) in whites, and fibrinogen gamma (EGG) rs2066865 (OR 1.91, p = 0.01) in Hispanic Americans. SNP in these genes showed association with venous thrombosis risk in whites: MTHFR rs1801131 (OR 1.51. p = 0.01), MTHFR rs1801133 (OR 0.70, p = 0.04), FVL rs6025 (OR 2.69, p = 0.002), and EGG rs2066865 (OR 1.49, p = 0.02) in whites. A SNP in FGG rs2066865 (OR 2.19, p = 0.003) demonstrated association with arterial thrombosis risk in Hispanics. Conclusion. Our results implicate specific genetic risk factors for thrombosis in patients with SLE and suggest that genetic risk for thrombosis differs across ethnic groups. (First Release June 15 2012; J Rheumatol 2012;39:1603-10; doi:10.3899/jrheum.111451)
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