AB0132 Genetic polymorphisms of fas and fasl apoptotic proteins as susceptibility factors to systemic lupus erythematosus in brazilian patients
Authors: N. Glesse, O. A. Monticielo, L. M. G Paim, R. M. Xavier, J. C. T. Brenol, P. Vianna, J. A. B. Chies
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is an autoimmune chronic inflammatory disease that affects multiple organs and systems, presenting a wide range of clinical manifestations. Immunological, environmental, hormonal and genetic factors may contribute to disease. Apoptosis is a highly regulated programmed cell death mechanism and it is a critical event for the normal biological function of multicellular organisms. It is regulated by different pathways involving genes that promote or inhibit this process. The death receptors and their specific ligands, such as FAS and FAS Ligand (FASL), are among the molecules of main importance for apoptosis. FAS receptor interacts with its natural ligand FASL to initiate the death signal cascade, which results in apoptotic cell death. Polymorphisms in the promoter region of these genes may deregulate the activity, affecting the expression of FAS and FASL proteins. An increased or decreased apoptosis, as well as a reduced clearance of apoptotic cells may lead to an increased exposure of nucleosomes to the immune system, identified as very important autoantigens for SLE triggering. <h3>Objectives</h3> Our objective was to evaluate the role of two promoter functional polymorphisms, <i>FAS -1377</i> (rs2234767) and <i>FASL -844</i> (rs763110) in SLE predisposition. <h3>Methods</h3> This study included 370 SLE patients followed at the Division of Rheumatology of Hospital de Clínicas de Porto Alegre, and 491 healthy blood donners. <i>FAS -1377</i> and <i>FASL -844</i> variants were genotyped by PCR-RFLP. <h3>Results</h3> Analyses were performed subdividing the individuals according to their ethnic origin. Among African-derived individuals, a higher frequency of the <i>FASL -844CC</i> genotype and of the <i>-844C</i> allele was observed among SLE patients as compared to controls (20% vs. 7%, p=0.0021; OR 4.33 CI 95% 1.78 – 10.46 and 45% vs. 29%, p=0.0003; OR 1.99 CI 95% 1.35 – 2.91, respectively). In European-derived group, a statistically significant difference was found in allelic and genotypic frequencies between SLE patients and matched controls (p=0.005), however the genotypic frequencies in control individuals were not in Hardy-Weinberg equilibrium. <h3>Conclusions</h3> Our data suggest that the higher frequency of the <i>FASL -844C</i> allele in African-derived SLE patients, related to a higher promoter activity and basal expression of FASL, may be contributing to increased apoptosis in this group. These findings indicate a possible role of the <i>FASL -844T/C</i> polymorphism in susceptibility of SLE among African-derived. <h3>References</h3> Kyttaris VC, Krishnan S and Tsokos GC (2006) Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function. Autoimmunity 39:705-709. Navratil JS and Ahearn JM (2001) Apoptosis, clearance mechanisms, and the development of systemic lupus erythematosus. Curr Rheumatol Rep 3:191-198. Lee YH, Kim YR, Ji JD, Sohn J and Song GG (2001) Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in systemic lupus erythematosus. J Rheumatol 28:2008-2011. <h3>Disclosure of Interest</h3> None Declared