Glutathione S-transferase M1 and T1 genetic polymorphism in Egyptian patients with nonsegmental vitiligo

Abstract

Oxidative stress and accumulation of free radicals might play a role in the pathogenesis of vitiligo. Glutathione S-transferase (GST) is a multigene family of enzymes that detoxify oxidative stress products. In this study, genotyping by multiplex PCR of GSTM1 and GSTT1 in 101 women with nonsegmental vitiligo vulgaris and 101 age-matched healthy female volunteers showed that only the GSTM1 null genotype (P=0.04) was significantly overexpressed in patients with vitiligo. Analysis of the combined effect of GSTM1 and GSTT1 genotyping identified a significant association of risk for vitiligo with the GSTT1/GSTM1 double-null type only (P=0.01; OR=2.69; 95% CI 1.12-6.46). Age of onset of vitiligo was significantly earlier in patients with the T1 null genotype (P<0.01) and those with the T1-/M1+ and T1-/M1- combined genotypes (P<0.01 and P=0.01, respectively). In conclusion, the GSTM1 gene and the GSTM1/GSTT1 double-null genotype may be a risk factor for vitiligo in Egyptian patients. Inability to cope with oxidative stresses because of GST deficiency may cause early disease onset.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients

“…We were not able to compare our results to the two previous Egyptian reports as, Abd Rabou et al , in 2011 [ 10 ] , did not report such a comparison whereas Bassiouny and Khorshied, in 2013 11 , performed their study with female patients only. Whether our results denote that males and females have different underlying mechanisms leading to their risk of vitiligo, or that it is due to a bias in the selection of cases, or that there was a relatively limited number of patients, is not apparent.…”

“…In the total of 122 patients enrolled in this study, the frequency of the GSTM1/GSTT1 double null genotype was 9.8% while the frequency of GSTM1 null genotype was 52.5% and that of GSTT1 null genotype was 51.6%. The previous Egyptian studies done on vitiligo patients demonstrated 18.8% for GSTM1/T1 double null genotype, 56.4% for GSTM1 null and 30.7% for GSTT1 null 11 and 30% for GSTM1/T1 double null genotype, 52.5% for GSTM1 null and 57.5 % for GSTT1 null. 10…”

“…The objectives of this study were to analyze the frequency of GSTM1/T1 genotypes and to determine whether a GST polymorphism is a predisposing factor to generalized vitiligo. Furthermore, we investigated the hypothesis presented by "Bassiouny and Khorshied", 2013 11 that Egyptian patients with vitiligo who demonstrate the GSTT1/GSTM1 double null polymorphism together with the absence of the GSTM1 gene are at increased risk of having the disease.…”

“…Subsequently, several epidemiological studies have aimed to evaluate this association in diverse ethnicities, including two studies performed with an Egyptian population. 8 - 11 However, no clear consensus was reached. The studies until now performed with Egyptian patients besides being very scarce, had contradictory results.…”

Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

“…A decreased expression of MPO, GST, and CAT was reported, and GST polymorphism displayed excess GSTM1 null and GSTT1/GSTM1 double-null type [281, 282]. An involvement of MDF in vitiligo was suggested by altered OXPHOS lipid-dependent subunits [283].…”