Genetic risk factors for thrombosis in systemic lupus erythematosus.
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.


CONCLUSIONS
Our results implicate specific genetic risk factors for thrombosis in patients with SLE and suggest that genetic risk for thrombosis differs across ethnic groups.
UCSF Division of Rheumatology, San Francisco, CA 94143, USA.
Rachel
R
Kaiser
Yonghong
Y
Li
Monica
M
Chang
Joseph
J
Catanese
Ann B
AB
Begovich
Elizabeth E
EE
Brown
Jeffrey C
JC
Edberg
Gerald
G
McGwin
Graciela S
GS
Alarcón
Rosalind
R
Ramsey-Goldman
John D
JD
Reveille
Luis M
LM
Vilá
Michelle A
MA
Petri
Robert P
RP
Kimberly
Kimberly E
KE
Taylor
Lindsey A
LA
Criswell
D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013927:Thrombosis / Q000150:complications / Q000235:genetics*