Association of acid phosphatase locus 1*C allele with the risk of cardiovascular events in rheumatoid arthritis patients

A 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.No 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).Our data show that the ACP1*C allele influences the risk of CV events in patients with RA.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]. On the other hand, increased cardiovascular (CV) mortality is observed in patients with RA. This is the result of accelerated atherogenesis [2-4].Acid phosphatase locus 1 (ACP1) is a gene located on chromosome 2p25 that encodes a low molecular weight phosphotyrosine phosphatase (LMW-PTP), which presents two main enzymatic activities: phosphoprotein tyrosine phosphatase and flavin mononucleotide phosphatase [5]. Two different isoenzymes of LMW-PTP have been described: 'fast' (also noted as ACP1-F(fast), isoform 1, IF1, HCPTP-A) and 'slow' (also noted as ACP1-S(slow), isoform 2, IF2, HCPTP-B), that arise through alternative splicing mechanisms, in which either exon 3 or exon 4 is excised and the other retained respectively [5,6]. These two LMW-PTP isoenzymes have different