Novel genetic association of the VTCN1 region with rheumatoid arthritis.
OBJECTIVE
Based upon findings in juvenile idiopathic arthritis, the genetic contribution of the VTCN1 region to rheumatoid arthritis (RA) susceptibility and anticitrullinated protein antibody (ACPA) status was investigated. VTCN1 is known to play a pivotal role in regulation of the immune system and, in soluble form, has previously been associated with higher disease activity.


METHODS
Ten VTCN1 polymorphisms were genotyped in 1237 Dutch patients with RA and 1055 healthy controls. Significant findings were replicated in two independent RA populations of northern European descent consisting of 2826 patients and 2122 healthy controls. Allele distribution was analysed using a χ(2) test and combined analysis of all studies was performed using the Mantel-Haenszel fixed effects method.


RESULTS
A significant association with two polymorphisms was observed in the Dutch RA population. Replication of these findings showed an overall significant association with rs4376721 and rs10923217 (OR 1.13, 95% CI 1.03 to 1.24, p=0.013 and OR 0.78, 95% CI 0.67 to 0.91, p=0.0011, respectively). Stratification for ACPA status revealed an association in the ACPA-negative subset for rs4376721 (OR 1.19, 95% CI 1.05 to 1.35, p=0.0071), while no overall significance could be observed in the ACPA-positive population. rs10923217 was associated with both subsets of the disease.


CONCLUSIONS
These results indicate a novel genetic association with the VTCN1 region in RA susceptibility.
Department of Rheumatology, Leiden University Medical Center, The Netherlands. n.a.daha@lumc.nl
Nina A
NA
Daha
Benedicte A
BA
Lie
L A
LA
Trouw
Gerrie
G
Stoeken
Joris J M
JJ
Schonkeren
Bo
B
Ding
Tore K
TK
Kvien
Marco W
MW
Schilham
Leonid
L
Padyukov
T W J
TW
Huizinga
Rene
R
Toes
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics*
D001323:Autoantibodies; D010456:Peptides, Cyclic; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; C487763:cyclic citrullinated peptide