The glutathione S-transferase T1 deletion is associated with susceptibility to multiple sclerosis

Živković, Maja; Zivotic, Ivan; Dinčić, Evica; Stojković, Ljiljana; Vojinović, Slobodan; Stanković, Aleksandra

doi:10.1016/j.jns.2013.07.001

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…Another results from study of patients with North-European [11] or Greek origin [13] did not identify any relevant association of these changes with multiple sclerosis. Our results indicate the importance of GSTT1 null genotype (p=0.04) and double null genotype GSTM1, GSTT1 (p=0.006) for MS. Higher prevalence of null genotypes in control group suggests the protective role of these changes for MS onset and development, which is not in line with previously mentioned data [12]. We obtained significant result in GSTT1 null genotype and its association with mid-rate progression (p=0.05), also the frequency of GSTM1, GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (p=0.05) and middle (p=0.045).…”

Section: Discussioncontrasting

confidence: 72%

“…The aim of our work was to analyse selected genetic changes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1, rs10735781 EVI5) in a group of Slovak MS patients and to shed light on their potential importance for disease onset or disability rate. Certain genetic variations of glutathione-S-transferases with the negative influence on enzyme functions have been previously indicated as associated with multiple sclerosis, but their role in the etiopathogenesis of MS still remains controversial [10][11][12]. In group of 455 Serbian MS patients, GSTT1 null genotype and GSTM1, GSTT1 double null genotypes were observed in significantly higher frequency (p<0.0001 and p<0.05) when compared to 366 healthy people [12].…”

Section: Discussionmentioning

confidence: 99%

“…Certain genetic variations of glutathione-S-transferases with the negative influence on enzyme functions have been previously indicated as associated with multiple sclerosis, but their role in the etiopathogenesis of MS still remains controversial [10][11][12]. In group of 455 Serbian MS patients, GSTT1 null genotype and GSTM1, GSTT1 double null genotypes were observed in significantly higher frequency (p<0.0001 and p<0.05) when compared to 366 healthy people [12]. Another results from study of patients with North-European [11] or Greek origin [13] did not identify any relevant association of these changes with multiple sclerosis.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

Hanysova

Čierný

Kurča

et al. 2017

Acta Medica Martiniana

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A b s t r a c tObjective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5) to the risk of multiple sclerosis (MS) development and find out the possible association with disease disability progression rate.Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups -slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR.Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04) and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 -0.74; p=0.006) are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 -0.97; p=0.05). Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 -0.98; p=0.05) and middle (OR 0.33; p=0.045). We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression.Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

Hanysova

Čierný

Kurča

et al. 2017

Acta Medica Martiniana

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“…2 Although GSTP1 polymorphisms were not identified as possible susceptibility genes by genome-wide association studies, we explored a possible relationship between GSTP1 polymorphisms and allelic gene variants and the risk of MS due to the possible role of oxidative stress and lipid peroxidation in the pathogenesis of MS 1 and the upregulation of GSTP1 gene expression found in active demyelinating MS lesions. 3 Although two preliminary studies did not find a relationship between polymorphisms in either GSTM1 4,5 or GSTT1 5 and the risk for MS, another recent study showed an association between GSTT1 deletion and MS susceptibility 6 . Another study reported a relationship between GSTM1, GSTM3 and GSTP1, but not GSTT1, and the degree of disability in MS.…”

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confidence: 99%

The GSTP1 gene variant rs1695 is not associated with an increased risk of multiple sclerosis

et al. 2014

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We analyzed the allelic and genotypic frequencies of the glutathione-S-transferase P1 (GSTP1) rs1695 single nucleotide polymorphism (SNP) in 290 patients with multiple sclerosis (MS) and in 310 healthy controls. We found no significant association between the rs1695 variant and MS. Among MS patients, there was no relationship between the rs1695 variant and either gender, clinical type of MS or the age of onset of MS. These results suggest that the GSTP1 rs1695 polymorphism is not a risk factor for MS.Genome-wide association studies in samples from MS patients have identified more than 100 loci with genome-wide significance, but most of these loci had a modest odds ratio (OR) in the range of 1.1-1.3; only HLA (especially the HLA-DRB1*15:01 haplotype) had a strong association with MS risk. Glutathione S-transferases (GSTs) are a superfamily of dimeric phase 2 metabolic enzymes that catalyze the conjugation of reduced glutathione with electrophilic groups of carcinogens, herbicides/pesticides, and other compounds. GSTP1 also plays a role in inflammatory processes (http://www.ncbi.nlm.nih.gov/ pubmed/23596995). In humans, the GSTs are divided into a number of major classes that have distinct substrate specificities and tissue distributions. Polymorphisms in the GSTM1, GSTP1 and GSTT1 genes are known to alter gene function. The rs1695 variant of the GSTP1 gene (chromosome 11q13; Gene identity 2950, MIM 134660; http://www.ncbi.nlm.nih.gov/gene/2950) causes an amino-acid substitution and reduces the catalytic activity of the enzyme (http://www.ncbi.nlm.nih.gov/pubmed/ 9600848, http://www.ncbi.nlm.nih.gov/pubmed/16488119 and http://www.ncbi.nlm.nih.gov/pubmed/22401947). The rs1695 variant is the only non-synonymous polymorphism of the GSTP1 gene with a significant allele frequency in human populations and minor allele frequencies ranging from 17% to 44% (http://browser.1000genomes.org/Homo_sapiens/Variation/ Population?db5core;r511:67352189-67353189;v5rs1695;vdb 5variation;vf521985). The frequency of the GSTP1 rs1695 variant is nearly 35% in the Spanish population. 2Although GSTP1 polymorphisms were not identified as possible susceptibility genes by genome-wide association studies, we explored a possible relationship between GSTP1 polymorphisms and allelic gene variants and the risk of MS due to the possible role of oxidative stress and lipid peroxidation in the pathogenesis of MS 1 and the upregulation of GSTP1 gene expression found in active demyelinating MS lesions.3 Although two preliminary studies did not find a relationship between polymorphisms in either GSTM1 4,5 or GSTT1 5 and the risk for MS, another recent study showed an association between GSTT1 deletion and MS susceptibility 6 . Another study reported a relationship between GSTM1, GSTM3 and GSTP1, but not GSTT1, and the degree of disability in MS. Alexoudi et al.8 reported a similar distribution of GSTP1 genotypes in MS patients and controls but a higher frequency

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“…Several studies have examined associations between GSTT1 and GSTT1 polymorphisms and ADs, but the results reported are contradictory, possibly because of the low statistical power of individual studies (LEE et al, 2015). While some authors suggest that there is an association of GSTT1 and GSTM1 polymorphisms and these diseases (MANN et al, 2000;ŽIVKOVIĆ et al, 2013), other authors indicate that there is no association between them (STAVROPOULOU et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Association of GSTT1 and GSTM1 gene polymorphisms with susceptibility to autoimmune diseases: A preliminary study

Grujičić¹,

Radović-Jakovljević²,

Mihaljevic³

et al. 2018

Kragujevac J Science

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Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens. The aim of this study was to detrmine how polymorphisms of glutathione S-transferases T1 and M1 (GSTT1 and GSTM1) genes influences on the occurrence of two autoimmune diseases: multiple sclerosis (MS) and Hashimoto's thyroditis (HT). A multiplex polymerase chain reaction (PCR) was used to detect the deletions in GSTT1 and GSTM1 genes. Our results showed that patients with ADs had significantly higher (p < 0.05) frequency of GSTM1 null genotype compared to controls (44.4% vs. 0.0%, respectively). However, the homozygous deletion of both analyzed genes (GSTT1 null/GSTM1 null) showed no significant differences between these genotypes in the patients and controls (11.1% vs 0.0%, respectively). Our results showed that observed differences in the distribution of GSTT1 and GSTM1 null genotype in patients depending on the diagnosis (MS or HT) when compared to the same frequency of genotypes in control, were not statistically significant (p > 0.05). This study suggests the potential role of GSTM1 deletion on ADs susceptibility, but on the other hand this study should be repeated in other patients with the same or similar diagnosis of ADs.

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The glutathione S-transferase T1 deletion is associated with susceptibility to multiple sclerosis

Cited by 15 publications

References 34 publications

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

The GSTP1 gene variant rs1695 is not associated with an increased risk of multiple sclerosis

Association of GSTT1 and GSTM1 gene polymorphisms with susceptibility to autoimmune diseases: A preliminary study

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