Genetic variants in the prediction of rheumatoid arthritis.
OBJECTIVE
To determine whether the currently known genetic risk factors for rheumatoid arthritis (RA) improve the prediction of the development of RA compared to prediction using clinical risk factors alone in patients with undifferentiated arthritis (UA).


METHODS
Five hundred and seventy early UA-patients included in the Leiden Early Arthritis Clinic cohort, previously used to derive a clinical prediction rule, were used to explore the additional value of genetic variants. The following genetic variants were assessed HLA-DRB1 shared epitope (SE) alleles, rs2476601 (PTPN22), rs108184088 (TRAF1-C5), rs7574865 (STAT4), rs3087243 (CTLA4), rs4810485 (CD40), rs1678542 (KIF5A-PIP4K2C), rs2812378 (CCL21), rs42041 (CDK6), rs4750316 (PRKCQ), rs6684865 (MMEL1-TNFRSF14), rs2004640 (IRF5), rs6920220 and rs10499194 (TNFAIP3-OLIG3), interactions between HLA-SE alleles and rs2476601 (PTPN22) and between HLA-SE alleles and smoking. The area under the receiver operator curve (AUC) was used as measure of the discriminative ability of the models.


RESULTS
The AUC of a model consisting of genetic variants only was low, 0.536 (95% CI 0.48 to 0.59). The AUC of the model including genetic and clinical risk factors was not superior over the AUC of the clinical prediction rule (0.889, 95% CI 0.86 to 0.95 and 0.884, 95% CI 0.86 to 0.92).


CONCLUSIONS
In a population at risk, information on currently known genetic risk factors for RA does not improve prediction of risk for RA compared to a prediction rule based on common clinical risk factors alone.
van der Helm-van Mil
Annette H M
AH
Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands. avdHelm@lumc.nl
Toes
René E M
RE
Huizinga
Tom W J
TW
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D018450:Disease Progression; D004812:Epidemiologic Methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains