Association of mannose-binding lectin gene polymorphisms with antiphospholipid syndrome, cardiovascular disease and chronic damage in patients with systemic lupus erythematosus.
OBJECTIVE
To investigate the association of mannose-binding lectin (MBL)-deficient genotypes with cardiovascular disease in a large series of patients with systemic lupus erythematosus (SLE).


METHODS
A total of 114 patients diagnosed with SLE were included in the study. MBL polymorphisms were investigated by sequencing-based DNA typing of the promoter and exon 1 of the MBL2 gene. The genotypes 0/0, 0/XA and XA/XA were considered as MBL-low genotypes.


RESULTS
A higher prevalence of cardiovascular disease was observed in patients carrying MBL-low genotypes compared with those carrying MBL-high genotypes [30 vs 9%, P = 0.012, odds ratio (OR) 4.54, 95% confidence interval (CI) 1.20-16.46]. Patients with MBL-low genotypes also presented higher mean values for total cholesterol (228.6 vs 202.3 mg/dl, P = 0.017) and low-density lipoprotein (LDL) cholesterol (139.9 vs 121.9 mg/dl, P = 0.045), a higher frequency of chronic renal failure (30 vs 4%, P = 0.001), vasculitis (30 vs 11%, P = 0.043), heart valve lesions (71 vs 32%, P = 0.026), cardiac valve dysfunction (57 vs 7%, P = 0.0004) and associated APS (39 vs 12%, P = 0.005), a higher mean Systemic Lupus International Collaborating Clinics score (2.09 vs 1.26, P = 0.029) and a lower prevalence of low C4 levels (43 vs 71%, P = 0.015). Multivariate analysis of genetic, clinical and immunological variables showed that only antiphospholipid syndrome (APS) was independently associated with cardiovascular events (P = 0.001).


CONCLUSIONS
Although the prevalence of cardiovascular disease in our SLE patients carrying MBL-deficient genotypes was 3.3 times higher than in patients with non-deficient genotypes, only APS was independently associated with cardiovascular events. This suggests that the higher frequency of thrombotic events in SLE patients carrying MBL-deficient genotypes might be related to coexisting APS.
Font
J
J
Department of Autoimmune Diseases, Hospital Clínic, C/Villarroel, 170 08036-Barcelona, Spain.
Ramos-Casals
M
M
Brito-Zerón
P
P
Nardi
N
N
Ibañez
A
A
Suarez
B
B
Jiménez
S
S
Tàssies
D
D
García-Criado
A
A
Ros
E
E
Sentís
J
J
Reverter
J-C
JC
Lozano
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016736:Antiphospholipid Syndrome / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D002648:Child; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin