In Lupus, Genetic Risk Factors Associated With Thrombosis

Specific genetic risk factors for thrombosis are associated with thrombosis in patients with systemic lupus erythematosus (SLE). Genetic risk for thrombosis may differ across ethnic groups.

Kaiser and associates investigated whether genetic variants implicated in thrombosis pathways are associated with thrombosis in 2 ethnically diverse SLE cohorts. The discovery cohort included 1698 patients enrolled in the University of California, San Francisco, Lupus Genetics Project, and the replication cohort had 1361 patients enrolled in the PROFILE cohort. Single nucleotide polymorphisms (SNPs) 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.

A thrombotic event was experienced by 23% of patients with SLE in the discovery cohort. SNPs in these genes showed association with thrombosis risk overall in the discovery or replication cohorts and were assessed using meta-analytic methods: factor V Leiden (FVL) rs6025 and methylenetetrahydrofolate reductase (MTHFR) rs1801133 in white persons and fibrinogen gamma (FGG) rs2066865 in Hispanic Americans. Association with venous thrombosis risk in whites was shown in these SNPs: MTHFR rs1801131, MTHFR rs1801133, FVL rs6025, and FGG rs2066865. An SNP in FGG rs2066865 demonstrated association with arterial thrombosis risk in Hispanics.