Age- and gender-independent association of glutathione S-transferase null polymorphisms with chronic myeloid leukemia

Muddathir, Abdel Rahim Mahmoud; Abdallah, Elharam Ibrahim; Khabour, Omar F.; Abdelgader, Ream Elzain; Elgari, Mahmoud Mohamed

doi:10.17305/bjbms.2019.4176

Cited by 8 publications

(8 citation statements)

References 37 publications

(47 reference statements)

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“…Therefore, the GSTT1 genotype may be a protective factor for CML, whilst the null genotype showed an association with the development of CML. The above findings were in agreement with a recent study conducted in Sudan (Muddathir et al, 2019). Many studies have focused on the relationship between GSTT1 polymorphism and the risk of CML in diverse ethnic groups (Bajpai et al, 2007;Al-Achkar et al, 2014;Kassogue et al, 2015).…”

Section: Genotypessupporting

confidence: 93%

“…Interestingly, no association between GSTM1 null genotype and the risk of CML was found here: (OR =0.975, 95% CI: 0.578-1.584; p-value = 0.863). However, Muddathir and his co-workers found that GSTM1 null genotype was associated with increased risk of CML among Sudanese (Muddathir et al, 2019). This is not unexpected because Sudan is multiethnic with an admixture of Arab and African lineages which may be associated with differences in genetic makeup.…”

Section: Genotypesmentioning

confidence: 99%

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Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Idris

Elderdery

Khalil

et al. 2020

Asian Pac J Cancer Prev

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Background: The development of cancer results from an imbalance between exposure to carcinogens and the capacity of various enzyme systems engaged in activation or in the detoxification of xenobiotics. The aim of the present study is to investigate the association of GSTP1, GSTM1 and GSTT1 gene polymorphisms in susceptibility to Chronic Myeloid Leukaemia (CML). Methods: A total of 200 CML patients and 100 controls were enrolled in a case-control study with GSTM1 and GSTT1 analysis with PCR and GSTP1 analysis with PCR-RFLP. Results: The GSTT1 null genotype was significantly higher among CML patients suggesting that this genotype is associated with an increased risk of CML. It was found in 42% of cases as compared with 21% of the controls, (OR =2.78, 95% CI: 1.59-4.85; p-value =0.000). The presence of the GSTT1 genotype may thus be considered a protective factor for CML. The frequency of individuals carrying GSTM1 null genotype was slightly higher in the control group but this difference was not statistically significant. The GSTM1 null genotype was present in 35% of control cases and 34% of the CML patients, (OR=0.975, 95%CI: 0.58-1.58;p-value=0.863). Individuals with a combined GSTM1 null/GSTT1null genotype had an estimated 2.85-fold increased risk of CML, but no associated risk between GSTP1 Ile 105 Val polymorphism and CML was found (OR=1.99, 95% CI: 0.40-9.32; p-value = 0.417). Conclusions: No association between GSTP1 and GSTM1 with susceptibility to CML was found. GSTT1 genotype may be a protective factor for CML, while the null genotype shows association with developing CML.

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Section: Genotypessupporting

confidence: 93%

Section: Genotypesmentioning

confidence: 99%

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Idris

Elderdery

Khalil

et al. 2020

Asian Pac J Cancer Prev

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“…Therefore, identification of these genes in our antiretroviral-prescribed patients could facilitate the determination of higher-risk groups. The frequency of the double deletion found in our population 11.2% was lower than those reported in Ivory Coast 14.3% [24], Ghana 16.66% [26], Morocco 15.5% [27], Egypt 16.25% [28], Tunisia 18% [28] and Sudan 32.9% [29], but higher than that seen in Algeria 7.31% [30] and Namibia 3% [31]. The distribution of the mutant allele G in GSTP1 gene observed in our population 49.76% was statistically comparable to that reported in the Gambian population 53.6%, (p = 0.2).…”

Section: Discussioncontrasting

confidence: 69%

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

et al. 2019

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Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

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“…The results of the study by Hamed et al in 2019 showed different results from ours, namely there was an insignificant difference in the mean number of leukocytes in the TET2 gene polymorphism rs34402524 in the LGK population (p = 0.07). Different results were also reported by Muddathir et al in 2019 which showed that there was no difference in the mean number of leukocytes in the GSTT1 and GSTM1 polymorphisms (p = 0.254 and p = 0.797) [8].…”

Section: Discussionmentioning

confidence: 58%

Effects of the FOXO3a rs 4946936 Gene Polymorphism on the FOXO3a Transcription Factor in Chronic Granulocytic Leukemia Patients

Wardhani

Susianti²,

Rahayu³

et al. 2021

Open Access Maced J Med Sci

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Introduction : FOXO3a has an important role in the maintenance of leukemic stem cells. BCR-ABL inhibition therapy by TKI dasatinib aims to reduce the phosphorylation of the transcription factor FOXO3a, promote localization of FOXO3a in the nucleus and restore transcriptional activity. However, some studies showed that the TKI dasatinib, in addition to increase the relocation of Foxo3a to the intranuclear, also increase the expression of CDKN1c/p57 and Bcl6 genes that became the down target for Foxo3a intra nucleus ATM. Therefore, current therapy is mostly directed at personalized therapy (personalized medicine). The aim of this study was to investigate the effect of the FOXO3a rs4946936 gene polymorphism on the Foxo3a transcription factor in chronic granulocytic leukemia patients treated with Imatinib mesylate. Method : This is a cross-sectional study in patients with chronic granulocytic leukemia (CGL) with positive Bcr-ABL. The aim was to prove the effect of the FOXO3a gene polymorphism rs4946936 on the Foxo3a transcription factor. The data analysis test used was a correlation test and a regression test. Result : There were three polymorphisms of the FOXO3a gene, namely CC polymorphism, TC polymorphism, and TT polymorphism with a p-value of 0.026 and an r of 0.287, so it can be concluded that there was a significant correlation between the FOXO3a gene polymorphism and the Foxo3an transcription factor with a sufficient correlation value. In the regression test between the FOXO3a gene polymorphisms and the transcription factor FOXO3a, the p value was 0.029 and the B value was -0.294. This means that it has a negative and significant effect on the Foxo3a transcription factor variable. Conclusion : There was a significant correlation between the gene polymorphism FOXO3a rs4946936 and the transcription factor FOX3a. The FOXO3a gene polymorphism of the TT genotype had a negative effect on the FOXO3a transcription factor. The TT gene in the FOXO3a gene polymorphism was the most effective in reducing the FOXO3a transcription factor.

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Age- and gender-independent association of glutathione S-transferase null polymorphisms with chronic myeloid leukemia

Cited by 8 publications

References 37 publications

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Genetic Polymorphism of GSTP1, GSTM1 and GSTT1 Genes and Susceptibility to Chronic Myeloid Leukaemia

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

Effects of the FOXO3a rs 4946936 Gene Polymorphism on the FOXO3a Transcription Factor in Chronic Granulocytic Leukemia Patients

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