All polymorphisms studied in this paper [PMID: 24448344] , total : 2 polymorphisms

Title : Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene.

Abstract : OBJECTIVE: To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. METHODS: We analysed a total of 11 715 RA cases and 26 493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated. RESULTS: We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of >/=3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (p=1.29x10-5, ORACPA-negative 1.257 (1.135 to 1.394)) and less with ACPA positivity (p=0.0148, ORACPA-positive 1.072 (1.014 to 1.134)). The ORs between these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed (p=7.33x10-3). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated positively with ACPA production (p=0.005; r=0.483). CONCLUSIONS: We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association being greater in patients negative for ACPAs.

Author : Gazal S,Sacre K,Allanore Y,Teruel M,Goodall AH,Tohma S,Alfredsson L,Okada Y,Xie G,Constantin A,Balsa A,Kawasaki A,Nicaise P,Amos C,Rodriguez-Rodriguez L,Chioccia G,Boileau C,Zhang J,Vittecoq O,Barnetche T,Gonzalez Gay MA,Furukawa H,Cantagrel A,Le Loet X,Sumida T,Hurtado-Nedelec M,Richez C,Chollet-Martin S,Schaeverbeke T,Combe B,Khoryati L,Coustet B,El-Benna J,Siminovitch K,Plenge R,Padyukov L,Martin J,Tsuchiya N,Dieude P,

Source : Ann Rheum Dis. 2014 Jan 21. doi: 10.1136/annrheumdis-2013-204581.

No.	Polymorphism name	Gene Symbol	Entrez Gene ID
1	rs11439060	SPP1	6696
2	rs9138	SPP1	6696