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 (FGG) 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 FGG 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.
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 (FGG) rs2066865 (OR 1.91, p = 0.01) in Hispanic Americans. SNP in these genes showed association with venous thrombosis risk in whites: MTHFRrs1801131 (OR 1.51, p = 0.01), MTHFRrs1801133 (OR 0.70, p = 0.04), FVLrs6025 (OR 2.69, p = 0.002), and FGGrs2066865 (OR 1.49, p = 0.02) in whites. A SNP in FGGrs2066865 (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.
Authors: Ricard Cervera; Munther A Khamashta; Josep Font; Gian Domenico Sebastiani; Antonio Gil; Paz Lavilla; Juan Carlos Mejía; A Olcay Aydintug; Hanna Chwalinska-Sadowska; Enrique de Ramón; Antonio Fernández-Nebro; Mauro Galeazzi; Merete Valen; Alessandro Mathieu; Frédéric Houssiau; Natividad Caro; Paula Alba; Manuel Ramos-Casals; Miguel Ingelmo; Graham R V Hughes Journal: Medicine (Baltimore) Date: 2003-09 Impact factor: 1.889
Authors: Rachel Kaiser; Kimberly E Taylor; Yun Deng; Jian Zhao; Yonghong Li; Joanne Nititham; Monica Chang; Joseph Catanese; Ann B Begovich; Elizabeth E Brown; Jeffrey C Edberg; Gerald McGwin; Graciela S Alarcón; Rosalind Ramsey-Goldman; John D Reveille; Luis M Vila; Michelle Petri; Robert P Kimberly; Xuebing Feng; Lingyun Sun; Nan Shen; Wei Li; Jian-Xin Lu; Edward K Wakeland; Quan-Zhen Li; Wanling Yang; Yu-Lung Lau; Fei-Lan Liu; Deh-Ming Chang; Chack-Yung Yu; Yeong W Song; Betty P Tsao; Lindsey A Criswell Journal: Arthritis Rheum Date: 2013-01
Authors: R Robeva; D Tanev; S Andonova; M Nikolova; A Tomova; Ph Kumanov; A Savov; R Rashkov; Zl Kolarov Journal: Balkan J Med Genet Date: 2017-06-30 Impact factor: 0.519