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.

RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

“…Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6]. Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6].…”

“…Interestingly, it is noteworthy that MD patients demonstrated higher levels of GSTM1 transcripts relative to controls. Several studies have suggested that GSTM1 was associated with higher oxidative stress and increased risk for inflammatory diseases, including rheumatoid arthritis [50], systemic lupus erythematosus [51], ulcerative colitis [52], ankylosing spondylitis [5] and inflammatory bowel disease [6]. In addition, the increased frequency of HLA and GSTM1 plays an important role in the alloimmune responses of renal transplant recipients [53].…”

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution

“…Only one study is based on the enzymatic level of e-GST in scleroderma [84]. The other studies reported in the literature focused on GSTP1 polymorphisms (see Section 3.6 and Table 1) in pathologies like systemic lupus erythematosus [86], or are meta-analysis suggesting that the GSTP1 polymorphisms are not associated with the risk of rheumatoid arthritis [87]. Another study confirmed the lack of association between GSTP1 polymorphisms and multiple sclerosis [88].…”

Analysis of genetic polymorphisms of glutathione S‐transferase (GSTP1, GSTM1, and GSTT1) in Polish patients with systemic sclerosis

“…It has been evaluated that the null GSTM1 genotype is present in 40%‐60% of individuals of Caucasian origin, whereas the frequency of the null GSTT1 genotype in the Caucasian population is 10%‐20%. Moreover, carriers of the deletion of both genes ( GSTM1 (‐) and GSTT1 (‐)) account for about 8% …”