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AB0004 Psoriatic arthritis. genes involved in the mestizo population

Background Psoriatic Arthritis (PsA) is not a regular systemic autoimmune disease, many expert define it with autoinflammatory disease, resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion in approximately 10% of patients with skin psoriasis. It is important to identify novel genomic biomarkers associated with disease susceptibility but also able to detect early those patients with negative prognostic factors who may benefit from a more aggressive therapeutic approach. The over-expression of tumor necrosis factor (TNF)-a is a central element in the pathogenesis of psoriasis and psoriatic arthritis (2). The levels of TNF-alpha are under genetic control. An “A” at position -308 in the TNFA promoter has been shown to be associated with increased level of TNF-alpha expression and “A” at position -238 with a diminished level of TNF-α expression (3,4). Many authors consider that it is a disease only of Europeans descendants or Caucasians, however never be studied in mestizo population Objectives We investigate the potential association between the TNFA-238 G/A, TNFA-308 G/A, IL10 -1082 G/A,-819C/T, -592C/A polymorphisms and the Psoriatic Arthritis susceptibility. Methods The study included 52 PsA patients diagnosed by CASPAR criteria and 52 controls. The polymorphism of TNFA-308 G/A (rs1800629), TNFA-238 G/A (rs361525), IL10 -1082 G/A (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) were genotyped by single specific primers -polymerase chain reaction (SSP-PCR). All subjects were from an unrelated Venezuelan-Mestizo population with a history of ancestors, at least back to the third generation Results When comparing allele and genotype frequencies between the groups studied, no significant differences were observed for the TNFA-308 G/A (rs1800629) and IL10 -1082 G/A (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872). However, our results showed a significant decrease in the frequency of the TNF-238A allele among PsA patients compared to healthy individuals (3.8% vs. 10.57%, respectively, OR: 0.31, 95% CI: 0.92 -1.05, p: 0.02), suggesting that TNFA-238A allele may have a protective effect (Table 1). Conclusions This is the first genetic study carried out in Venezuelan mestizo patients with Psoriatic Arthritis to establish associations between genetic markers such as the polymorphisms of the promoter region of the TNFA and IL10 genes and the disease. In conclusion the TNFA-238 G/A polymorphism might play an important role in the development of Psoriatic Arthritis in Venezuelan mestizos and this association could not only clarify the different factors involved in a multifactorial disease, such as Psoriatic Arthritis, but also establish the relationship of these molecular markers with some clinical manifestations of the disease, which would allow in the future to determine the suitability or not to use some types of treatments, such as the use of anti-TNF therapy, for example. References Morales-Zambrano, et al. Int J Clin Exp Med. 2014; 7(9): 2605–2614. Bowes J, Barton A. Discov Med. 2010;10 (52):177–83. Liu Y, Helms C, et al. PLoS Genet, 2008;4(3): 1000041. Acknowledgements To bioanalyst Esther Guzmán, Marion DiMuro, Elena Flores and Mercedes Flores from the Clinica El Άvila and the University Hospital of Caracas (HUC/UCV), as well as Eva Salazar, Omar Balbas y Fernando Hernandez (IVIC). Disclosure of Interest L. A. Gutierrez-Gonzalez Grant/research support from: IIR/PFIZER, F. Herrera Grant/research support from: Grant Award (Pfizer), M. Fernandez Mestre: None declared