AB0211 Glutathione s-transferases and cytochrome p450 enzymes polymorphisms as susceptibility factors to systemic lupus erythematosus in southern brazilian patients
Authors: O.A. Monticielo, N. Glesse, P. Rohr, K. Kvitko, E.A. Souza, M.S. Ferreira, R. Calheiro, R.M. Xavier, J.C.T. Brenol, 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 presents a variety of clinical manifestationsand immunological abnormalities.There is evidence that immunological, environmental, hormonal and genetic factors may contribute to the occurrence of the disease. Genes and proteins involved in metabolism/detoxification of xenobiotics are often used as markers of susceptibility to the development of diseases whose etiology is related to exposure to environmental risk factors. Cytochrome P450 (CYP) enzymes are primarily responsible for phase I detoxification, in which activate the xenobiotic, making it more electrophilic and thus more reactive. The Glutathione S-transferases (GST) are phase II detoxifying enzymesand usually conjugate reduced glutathione with a variety of electrophilic compounds, such as reactive oxygen species, facilitating the excretion of toxic products. Polymorphismsin the <i>CYP</i> and <i>GST</i> genes can alter the expression and catalytic activity of enzymes, being responsible for interindividual differences regarding the capacity of xenobiotics biotransformation. <h3>Objectives</h3> To evaluate the influence of three <i>GST</i> polymorphisms (<i>GSTM1 null</i>, <i>GSTT1 null</i> and <i>GSTP1*Val</i>) and two <i>CYP</i> polymorphisms (<i>CYP1A1*2C</i> and <i>CYP2E1*5B</i>) in SLE predisposition. <h3>Methods</h3> This study included 370 SLE patients who were followed at the Division of Rheumatology of Hospital de Clínicas de Porto Alegre, and 329 healthy blood donors, both groups from Southern Brazil. The <i>CYP</i> polymorphisms were genotyped by PCR-RFLP, while the <i>GST</i> polymorphisms were genotyped by multiplex PCR and PCR-RFLP for <i>GSTP1</i>. <h3>Results</h3> Analyses were performed subdividing the individuals according to their ethnic origin. Among European-derived individuals, it was observed a lower frequency of <i>GSTP1*Val</i> heterozygous genotypes in SLE patients compared to controls (36% vs. 48%, p=0.0047; OR 0.63 CI 95% 0.43 - 0.93 in relation to <i>GSTP1*Ile/Ile</i> and OR 0.49 95% CI 0.26 - 0.92 in relation to <i>GSTP1*Val/Val</i>). In African-derived group, the <i>CYP2E1*5B</i> allele was significantly more frequent in patients than in matched controls (11% vs. 5%, p=0.038, OR 2.69 95% CI 1.00 - 8.42). We did not observe any association of the <i>CYP</i> and <i>GST</i> polymorphisms with the SLE clinical manifestations. <h3>Conclusions</h3> Our data suggest a protective role of the <i>GSTP1*105Ile/Val</i> heterozygous genotype in European-derived and a possible influence of the <i>CYP2E1*5B</i> allele in SLE susceptibility among African-derived. These findings may indicate new mechanisms of interaction among environment, genetics and the triggering of SLE. <h3>References</h3> Wilkinson Jt, Clapper ML: Detoxication enzymes and chemoprevention. Proc Soc Exp Biol Med 1997;216:192-200. Guecheva TN, Henriques JAP: Metabolismo de Xenobiόticos: Citocromo P450. Genética Toxicolόgica 2003:225-247. Manson JJ, Rahman A: Systemic lupus erythematosus. Orphanet J Rare Dis 2006;1:6. Crispin JC, Liossis SN, Kis-Toth K, et al.: Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med 2010;16:47-57. <h3>Disclosure of Interest</h3> None Declared