Genetically determined serum levels of mannose-binding lectin correlate negatively with common carotid intima-media thickness in systemic lupus erythematosus.
OBJECTIVE
Patients with systemic lupus erythematosus (SLE) have excess cardiovascular morbidity and mortality due to accelerated atherosclerosis that cannot be attributed to traditional cardiovascular risk factors alone. Variant alleles of the mannose-binding lectin gene (MBL2) causing low serum concentrations of functional mannose-binding lectin (MBL) are associated with SLE and development of atherosclerosis. Recent studies show that these variant alleles are associated with increased risk of arterial thrombosis and cardiovascular disease in patients with SLE. Intima-media thickness of the common carotid artery (ccIMT) is a validated noninvasive anatomic measure of subclinical atherosclerosis. In a cross-sectional study we examined the relation among ccIMT, MBL2 genotypes, and serum concentrations of MBL.


METHODS
The MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) and serum concentrations of MBL were determined in 41 outpatients with SLE. ccIMT was measured by means of ultrasonography. Traditional and nontraditional cardiovascular risk modifiers were assessed and controlled for.


RESULTS
Using nonparametric Mann-Whitney tests we found a significant difference in ccIMT between low-expressing (XA/XA+YA/YO+XA/YO+YO/YO) and high-expressing (YA/YA+YA/XA) MBL2 genotypes (p = 0.034). The difference in ccIMT remained significant in multivariable analysis adjusting for traditional and nontraditional cardiovascular risk modifiers (p = 0.049). ccIMT was negatively correlated to serum concentrations of MBL (Spearman rho = -0.33, p = 0.037). This relation also remained significant in multivariable analysis (p = 0.042).


CONCLUSIONS
In this group of SLE patients, MBL2 low-expressing genotypes and low serum levels of MBL were correlated with ccIMT, independent of the effects of traditional and nontraditional cardiovascular risk modifiers.
Troelsen
Lone N
LN
Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. lone.troelsen@mail.dk
Garred
Peter
P
Christiansen
Buris
B
Torp-Pedersen
Christian
C
Jacobsen
Søren
S
D000483:Alleles; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics; D017536:Carotid Artery, Common / Q000033:anatomy & histology*; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017539:Tunica Intima / Q000033:anatomy & histology*; D017540:Tunica Media / Q000033:anatomy & histology*
D037601:Mannose-Binding Lectin