Background Cardiovascular disease is an important complicationin patients with systemic lupus erythematosus (SLE). Variantalleles of the mannose-binding lectin gene are associated withSLE as well as with severe atherosclerosis. We determined whethermannose-binding lectin variant alleles were associated withan increased risk of arterial thrombosis among patients withSLE.
Methods Mannose-binding lectin alleles were genotyped by meansof a polymerase-chain-reaction assay in 91 Danish patients withSLE. Arterial and venous thromboses occurring after the diagnosisof SLE were assessed in a prospective study. Arterial and venousthromboses were confirmed by appropriate diagnostic methods.
Results Fifty-four patients had no mannose-binding lectin variantalleles (A/A genotype), 30 were heterozygous (A/O genotype),and 7 were homozygous (O/O genotype). During a median follow-upof 9.1 years, arterial thromboses (cerebral or myocardial infarctionor leg embolus) developed in 6 of the 7 patients with the O/Ogenotype, as compared with 18 of the 84 patients with the othertwo genotypes (hazard ratio, 5.8; 95 percent confidence interval,2.2 to 15.2; overall incidence, 26 percent). After correctionfor other known risk factors, the hazard ratio was 7.0 (95 percentconfidence interval, 1.9 to 25.4). Venous thromboses, whichoccurred in 14 patients, were statistically unrelated to themannose-binding lectin genotype.
Conclusions Among patients with SLE, homozygosity for mannose-bindinglectin variant alleles is associated with an increased riskof arterial thrombosis. The risk of venous thrombosis is notincreased, indicating that mannose-binding lectin has a specificrole in providing protection against arterial thrombosis.
Source Information
From the Department of Rheumatology, Bispebjerg Hospital (T.Ø., S.J.); the Department of Rheumatology, Hvidovre Hospital (T.Ø., S.J.); and the Department of Rheumatology (T.Ø., S.J.) and the Tissue Typing Laboratory, Department of Clinical Immunology (T.Ø., P.G., H.O.M.), Rigshospitalet, University of Copenhagen — all in Copenhagen, Denmark.
Address reprint requests to Dr. Jacobsen at the Department of Rheumatology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark, or at sj{at}dadlnet.dk.
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