Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis.
OBJECTIVE
To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA.


METHODS
MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively.


RESULTS
The prevalence of MBL variant alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin.


CONCLUSIONS
We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease process.
Jacobsen
Soren
S
Department of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark. sj@dadlnet.dk
Baslund
Bo
B
Madsen
Hans Ole
HO
Tvede
Niels
N
Svejgaard
Arne
A
Garred
Peter
P
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004247:DNA / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011111:Polymyalgia Rheumatica / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D005819:Genetic Markers; D015804:HLA-DR4 Antigen; D037601:Mannose-Binding Lectin; D004247:DNA