RT Journal Article
SR Electronic
T1 Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction in rheumatoid arthritis.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1654
OP 1661
VO 32
IS 9
A1 Juergen Graessler
A1 Michael Verlohren
A1 Anett Graessler
A1 Astrid Zeissig
A1 Eberhard Kuhlisch
A1 Steffi Kopprasch
A1 Hans-Egbert Schroeder
YR 2005
UL http://www.jrheum.org/content/32/9/1654.abstract
AB OBJECTIVE: Chondromodulin-II (ChM-II) is a cartilage-derived protein involved in cartilage and bone repair. A study of Japanese patients with rheumatoid arthritis (RA) implicated an association between a 172G --> A (Val58Ile) polymorphism and radiographic damage. We analyzed ChM-II for polymorphisms and investigated the association with radiographically assessed joint destruction in German patients with RA. Possible interactions with the shared epitope (SE) were examined. METHODS: DNA samples from 204 patients with RA, 81 patients with osteoarthritis, and 116 patients with gout, serving as controls, were sequenced. Radiographic damage was assessed by modified Larsen score. Allele and genotype frequencies between groups were compared by Cochrane-Armitage trend tests. RESULTS: Five missense mutations, one silent mutation, and 5 intronic polymorphisms were found. Allele and genotype frequencies were similar in both disease groups. Larsen scores were significantly higher in RA patients carrying the 172AA (Ile/Ile) genotype (Larsen 96.8), than in RA patients with the 172GA (Val/Ile; Larsen 69.5) or 172GG (Val/Val; Larsen 54.8; p = 0.001) genotypes. Odds ratios to develop more severe radiographic joint damage (Larsen score > 90; above 75th percentile) were 4 and 15.5 for the 172GA and 172AA genotypes, respectively. Presence of a 172A allele increased the risk for enhanced radiographic damage 3-fold. SE and ChM-II 172A alleles emerged as 2 independent risk factors. A potentiated interaction of these risk alleles could not be verified. CONCLUSION: Our data indicate that ChM-II Val58Ile polymorphism is associated with radiographic progression of joint destruction, particularly in German patients with RA negative for SE.