Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (<or=20 years) was particularly high among XA/XA homozygotes (17.4%) as compared to the rest of the patients (5.6%) (p=0.004). XA/XA carriers did have significantly higher risk of development of cutaneous manifestations (p=0.003) and pleuritis/pericarditis (p=0.013) as compared with the rest of the patients. These data indicate that MBL may act as a disease modifier in SLE patients through a mechanism to be identified.