The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. TIRA Group.
OBJECTIVE
To determine whether variant alleles of the mannose binding lectin (MBL) gene causing low serum concentrations of MBL are associated with increased susceptibility to rheumatoid arthritis (RA) and erosive outcome in an inception cohort of patients with early polyarthritis.


METHODS
MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 68 Danish patients with incident early polyarthritis observed for one year. The associations between MBL and specific HLA-DRB1 genotypes and disease outcomes were analyzed.


RESULTS
Among the patients with early polyarthritis 7.4% (5/68) and 41.2% (28/68) were homozygous and heterozygous for MBL variant alleles, compared with 2.8% (7/250) and 34.4% (86/250) of healthy controls (p = 0.09), while the corresponding figures in the patients with RA were 10% (5/50) and 42% (21/50) (p = 0.03), and in the patients with erosive RA 18.8% (3/16) and 35.3% (6/16), respectively (p = 0.004). Patients with early polyarthritis homozygous for MBL variant alleles had an increased risk of having erosive RA at inclusion by a factor of 4.7 (p = 0.02) and after one year by a factor of 3.6 (p = 0.04). MBL deficiency was associated with increased levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) at inclusion (p < 0.05). HLA-DRB1 alleles were not found to be associated with disease outcome.


CONCLUSIONS
MBL variant alleles appear to be weak susceptibility markers for RA, and patients with early polyarthritis and homozygous for MBL structural variant alleles have a higher risk of developing early erosive RA. These findings, together with the positive association between MBL variant alleles and the increased serum levels of IgM RF and CRP, point at the MBL gene as a relevant locus in the pathophysiology of RA.
Jacobsen
S
S
Department of Rheumatology, Hvidovre Hospital, Copenhagen University Hospital, Denmark. sj@dadlnet.dk
Madsen
H O
HO
Klarlund
M
M
Jensen
T
T
Skjødt
H
H
Jensen
K E
KE
Svejgaard
A
A
Garred
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000453:epidemiology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D037222:Collectins; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012217:Rheumatoid Factor / Q000097:blood; D012307:Risk Factors
D002352:Carrier Proteins; D037222:Collectins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007075:Immunoglobulin M; D012217:Rheumatoid Factor