Background: Self-immunization in systemic lupus is driven by defective in apoptosis. Fas, is an apoptosis-promoting cell surface receptor. The present study evaluate the possible association between APO-1/FAS Promoter (-670A/G) Polymorphism and sFAS level with susceptibility to lupus nephritis in SLE patients. Design and Methods: This study was performed on 88 female patients with SLE (mean age, 39.82 ± 10.16 years). 82 patients with lupus nephritis (mean age, 42.50 ± 6.65 years). 150 age and sex-matched person served as controls. All participants were genotyped for the APO-1/FAS Promoter (-670A/G) Polymorphism, manifestations and serum sFAS were correlated with the genotypes. Results: Serum sFAS was significantly higher in patients with -670 AA genotype compared to others. (-670A/G) AA genotype frequencies were significantly higher in the lupus nephritis and SLE patients groups compared with the controls and were associated with increased risk for lupus nephritis and SLE development (odds ratio, 4.08 and 1.91 respectively). Conclusions: The APO-1/FAS Promoter (-670A/G) A allele can be used as a genetic marker for lupus nephritis susceptibility in SLE and was associated with high sFAS level.
Lee, H.-S. and Bae, S.-C. (2010) What Can We Learn from Genetic Studies of Systemic Lupus Erythematosus? Implications of Genetic Heterogeneity among Populations in SLE. Lupus, 19, 1452-1459. http://dx.doi.org/10.1177/0961203310370350
Munoz, L.E., Van Bavel, C., Franz, S., Berden, J., Herrmann, M. and Van Der Vlag, J. (2008) Apoptosis in the Pathogenesis of Systemic Lupus Erythematosus. Lupus, 17, 371-375. http://dx.doi.org/10.1177/0961203308089990
Kanemitsu, S., Ihara, K., Saifddin, A., Otsuka, T., Takeuchi, T. and Nagayama, J. (2002) A Functional Polymorphism in Fas (C D95/APO-1) Gene Promoter Associated with Systemic Lupus Erythematosus. Journal of Rheumatology, 29, 1183-1188.
Cheng, J., Zhou, T., Liu, C., Shapiro, J.P., Brauer, M.J., Kiefer, M.C., et al. (1994) Protection from Fas-Mediated Apoptosis by Soluble Form of the Fas Molecule. Science, 263, 1759-1762. http://dx.doi.org/10.1126/science.7510905
Rudert, F., Visser, E., Forbes, L., Lindridge, E., Wang, Y. and Watson, J. (1995) Identification of a Silencer, Enhancer, and Basal Promoter Region in Human CD95 (Fas/APO-1) Gene. DNA and Cell Biology, 14, 931-937. http://dx.doi.org/10.1089/dna.1995.14.931
Huang, Q.R., Danis, V., Lassere, M., Edmonds, J. and Manolios, N. (1999) Evaluation of a New Apo-1/Fas Promoter Polymorphism in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients. Rheumatology, 38, 645-651. http://dx.doi.org/10.1093/rheumatology/38.7.645
Hao, J.H., Ye, D.Q., Zhang, G.Q., Liu, H.H., Dai, H., et al. (2006) Elevated Levels of Serum Soluble Fas Are Associated with Organ and Tissue Damage in Systemic Lupus Erythematosus among Chinese. Archives of Dermatological Research, 297, 329-332. http://dx.doi.org/10.1007/s00403-005-0616-2
Telegina, E., Reshetnyak, T., Moshnikova, A., Proussakova, O., Zhukova, A., Kuznetsova, A., et al. (2009) A Possible Role of Fas-Ligand-Mediated “Reserse Signalling” in Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus. Immunology Letters, 122, 12-17. http://dx.doi.org/10.1016/j.imlet.2008.10.003
Diecker, J.W.C., van der Vlag, J. and Berden, J.H.M. (2004) Deranged Removal of Apoptotic Cells: Its Role in the Genesis of Lupus. Nephrology Dialysis Transplantation, 19, 282-285. http://dx.doi.org/10.1093/ndt/gfg485
Moudi, B., Salimi, S., Mashhadi, F.F., Sandoughi, M. and Zakeri, Z. (2013) Association of FAS and FAS Ligand Genes Polymorphism and Risk of Systemic Lupus Erythematosus. The Scientific World Journal, 2013, Article ID: 176741.
Molin, S., Weiss, E.H., Ruzicka, T. and Messer, G. (2012) The FAS/CD95 Promoter Single-Nucleotide Polymorphism -670 A/G and Lupus Erythematosus. Clinical and Experimental Dermatology, 37, 425-427. http://dx.doi.org/10.1111/j.1365-2230.2011.04296.x
Kanemitsu, S., Ihara, K., Saifddin, A., Otsuka, T., Takeuchi, T. and Nagayama, J. (2002) A Functional Polymorphism in Fas (CD95/APO-1) Gene Promoter Associated with Systemic Lupus Erythematosus. Journal of Rheumatology, 29, 1183-1188.
Huang, Q.R., Morris, D. and Manolios, N. (1997) Identification and Characterization of Polymorphisms in the Promoter Region of Human Apo-1/Fas (CD95) Gene. Molecular Immunology, 34, 577-582. http://dx.doi.org/10.1016/S0161-5890(97)00081-3
Araste, J.M., Sarvestani, E.K., Aflaki, E. and Amirghofran, Z. (2010) Fas Gene Polymorphisms in Systemic Lupus Erythematosus and Serum Levels of Some Apoptosis-Related Molecules. Immunological Investigations, 39, 27-38. http://dx.doi.org/10.3109/08820130903401736
Lee, Y.H., Kim, Y.R., Ji, J.D., et al. (2011) Fas Promoter-670 Polymorphism Is Associated with Development of Anti-RNP Antibodies in Systemic Lupus Erythematosus. Journal of Rheumatology, 28, 2008-2001.
Man-Manlu, L.U., Ye, Q.-L., Feng, C.-C., Yang, J., Zhang, T., Li, J., Leng, R.-X., Pan, H.-F., Yuan, H. and Ye, D.-Q. (2012) Association of FAS Gene Polymorphisms with Systemic Lupus Erythematosus: A Case-Control Study and Meta-Analysis. Experimental and Therapeutic Medicine, 4, 497-502.
Hochberg, M.C. (1997) Updating the American College of Rheumatology Revised Criteria for the Classification of Systemic Lupus Erythematosus. Arthritis Rheumatology, 40, 1725. http://dx.doi.org/10.1002/art.1780400928