Abstract
IntroductionAcid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell. The aim of this study was to determine the contribution of ACP1 polymorphisms to susceptibility to rheumatoid arthritis (RA), as well as the potential contribution of these polymorphisms to the increased risk of cardiovascular disease (CV) observed in RA patients.MethodsA set of 1,603 Spanish RA patients and 1,877 healthy controls were included in the study. Information related to the presence/absence of CV events was obtained from 1,284 of these participants. All individuals were genotyped for four ACP1 single-nucleotide polymorphisms (SNPs), rs10167992, rs11553742, rs7576247, and rs3828329, using a predesigned TaqMan SNP genotyping assay. Classical ACP1 alleles (*A, *B and *C) were imputed with SNP data.ResultsNo association between ACP1 gene polymorphisms and susceptibility to RA was observed. However, when RA patients were stratified according to the presence or absence of CV events, an association between rs11553742*T and CV events was found (P = 0.012, odds ratio (OR) = 2.62 (1.24 to 5.53)). Likewise, the ACP1*C allele showed evidence of association with CV events in patients with RA (P = 0.024, OR = 2.43).ConclusionsOur data show that the ACP1*C allele influences the risk of CV events in patients with RA.
Highlights
Acid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell
LMW-PTP has been involved in the regulation of many growth factors such as platelet-derived growth factor receptor (PDGFR) [10], fibroblast growth factor receptor (FGFR) [11], insulin receptor (IR) [12,13] and EphA2 receptor, a ligand that binds to the Ephrin family of signaling molecules [14]
Taking into account the possible influence that ACP1 may have in the susceptibility to immune-mediated disorders and in the pathogenesis of the cardiovascular disease (CV) disease, in the present study we aimed to investigate the possible association of ACP1 alleles with the susceptibility to rheumatoid arthritis (RA) as well as whether ACP1 gene polymorphism may contribute to the increased risk of CV complications observed in patients with RA
Summary
Acid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell. Rheumatoid arthritis (RA) is a complex polygenic autoimmune inflammatory disease characterized by persistent synovitis and joint damage. Several genetic polymorphisms, such as HLA-DRB1, PTPN22, STAT4, TRAF1/C5 and TNFAIP3, have been implicated in the susceptibility to RA [1]. LMW-PTP is considered to play a key role as regulator of signaling pathways in receptor-stimulated immune cells [9]. LMW-PTP has been implicated in the regulation of ZAP70 Kinase (ζchain- associated protein kinase of 70 kDa) [15] playing a role in T-cell development and lymphocyte activation, enhancing signaling from the T cell antigen receptor [15]. LMW-PTP has been found to be a key mediator in the integrin signaling during cellular adhesion [9]
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