title: Genetic polymorphisms of glutathione S-transferases and cytochrome P450 enzymes as susceptibility factors to systemic lupus erythematosus in southern Brazilian patients.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that presents several clinical manifestations, affecting multiple organs and systems. Immunological, environmental, hormonal and genetic factors may contribute to disease. Genes and proteins involved in metabolism and detoxification of xenobiotics are often used as susceptibility markers to diseases with environmental risk factors. Cytochrome P450 (CYP) enzymes activate the xenobiotic making it more reactive, while the Glutathione S-transferases (GST) enzymes conjugate the reduced glutathione with electrophilic compounds, facilitating the toxic products excretion. CYP and GST polymorphisms can alter the expression and catalytic activity of enzymes. This study aimed to investigate the role of genetic variants of CYP and GST in susceptibility and clinical expression of SLE, through the analysis of GSTM1 null, GSTT1 null, GSTP1*Ile105Val, CYP1A1*2C and CYP2E1*5B polymorphisms. 371 SLE patients from Hospital de Clínicas de Porto Alegre and 522 healthy blood donors from southern Brazil were evaluated. GSTP1 and CYP variants were genotyped using PCR-RFLP and GSTT1 and GSTM1 variants were analyzed by multiplex PCR. Among European-derived individuals, a lower frequency of GSTP1*Val heterozygous genotypes was found in SLE patients when compared to controls (p = 0.005). In African-derived SLE patients, the CYP2E1*5B allelic frequency was higher in relation to controls (p = 0.054). We did not observe any clinical implication of the CYP and GST polymorphisms in patients with SLE. Our data suggest a protective role of the GSTP1*Ile/Val heterozygous genotype against the SLE in European-derived and a possible influence of the CYP2E1*5B allele in SLE susceptibility among African-derived individuals.
authors: Laboratory of Immunogenetics, Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Bento Gonçalves Avenue-9500, Campus do Vale., PO BOX 15053, Porto Alegre, RS, 91501970, Brazil.
authors: Nadine
authors: N
authors: Glesse
authors: Paula
authors: P
authors: Rohr
authors: Odirlei André
authors: OA
authors: Monticielo
authors: Tássia Flores
authors: TF
authors: Rech
authors: João Carlos Tavares
authors: JC
authors: Brenol
authors: Ricardo Machado
authors: RM
authors: Xavier
authors: Kátia
authors: K
authors: Kvitko
authors: José Artur Bogo
authors: JA
authors: Chies
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D001938:Brazil; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D044465:White People / Q000235:genetics; D015262:Xenobiotics
chemical_list: D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D017382:Reactive Oxygen Species; D015262:Xenobiotics; C569463:CYP1A1 protein, human; C413545:glutathione S-transferase T1