ASSOCIATION OF AN ANP32A POLYMORPHISM WITH HIGH BASRI SCORES IN ANKYLOSING SPONDYLITIS: A HYPOTHESIS GENERATING STUDY

Background: The relationship between inflammation and bone formation in Ankylosing Spondylitis (AS) is still unresolved. According to a view, bone formation results from an excessive repair response after damage to the joint has been produced by inflammation. An alternative hypothesis proposes that the two processes are parallel and secondary to unknown trigger events. Specific genetic factors favoring bone formation, which would be different from those that determine disease susceptibility but similar to the found in other diseases characterized by bone formation, have been specifically advocated in this second model. Objectives: We hypothesized that genetic variation in genes of the WNT pathway may be involved in the extent of new bone formation in AS. Methods: We have examined 21 SNPs in 9 genes in the WNT pathway selected because of their involvement in bone metabolism or bone diseases or in other chronic diseases (LRP5: rs3736228, rs599083, rs41494349; LRP4: rs6485702; LRP6: rs2302685, TCF7L2, rs3814570, rs7903146; FRZB: rs288326, rs7775; sFRP1: rs4736965; ANP32A: rs7164503; DKK1: rs1896373, rs1569198, rs10824351, rs11001553, rs11001721, SOST: rs7222683, rs1230397, rs865429, rs17742347, rs9303537). Samples and clinical information from 679 patients with AS were collected in a multicenter collection (n=417) and in two collections from individual hospitals (n=160 and 102). All patients were of Spanish ancestry. The total Bath Ankylosing Spondylitis Disease Activity Index (BASRI) was used to represent the degree of new bone formation. Genotyping was performed by minisequencing. Results were adjusted by gender and time since disease onset. Results: Only one of the SNPs was significantly different between patients with high and low BASRI, rs7164503 in ANP32A. Its minor allele was increased in the AS patients with BASRI ≥8 (O.R. =1.65, 95% C.I. =1.1- 2.4; P =0.010) when patients were stratified in two levels. A more detailed analysis with multinominal logistic regression showed that the frequency of the minor allele was increased in patients with BASRI >4 (OR=2.32, 95% C.I. =1.4-3.8; P =0.0011). Results were consistent in the three patient collections. The ANP32A gene encodes a leucine-rich repeat acidic nuclear protein involved in a complex network of protein-protein interactions including interference with canonical WNT signaling. The minor allele of rs7164503 has been found to protect from hip osteoarthritis. Conclusions: Our results suggest that ANP32A could have a role in the formation of new bone in AS, but this result requires replication given the limited statistical support obtained. References: 1. Lories RJ, Luyten FP, de Vlam K. Arthritis Res Ther. 2009;11:221 2. Valdes AM, et al. Arthritis Rheum. 2009;60:2046-54 Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 209Session: Genomics, genetics and epigenetics of rheumatic diseases (Poster Presentations )