Genetic Polymorphisms of Glutathione S-Transferase and Risk of Acute Myeloid Leukemia: Case-Control Study and Meta-Analysis
MIDDLE EAST JOURNAL OF CANCER
Authors: Boujmia, Oum Kaltoum Ait; Nadifi, Sellama; Dehbi, Hind; Kassogue, Yaya; Lamchahab, Mouna; Quessar, Asma
Abstract
Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk. Methods: The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML. Results: We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, GSTT1 null and GSTP1 Ile / Val et Val /Val genotypes had a higher risk of developing AML. The results of meta-analysis showed a positive association between GSTM1 null, GSTT1 null and Ile105Val GSTP1 polymorphisms and AML risk in East Asians, Caucasians, and mixed populations, respectively. Conclusion: GST gene polymorphisms may be risk factors for acute myeloid leukemia.
Glutathione S-Transferase Gene Polymorphisms and the Development of New-Onset Diabetes After Liver Transplant
EXPERIMENTAL AND CLINICAL TRANSPLANTATION
Authors: Musavi, Zahra; Moasser, Elham; Zareei, Neda; Azarpira, Negar; Shamsaeefar, Ali
Abstract
Objectives: The association between the glutathione S-transferase polymorphisms and the development of new-onset diabetes mellitus after liver transplant was studied. Materials and Methods: Peripheral blood samples were collected from 106 liver transplant patients divided into 2 groups: 52 with new-onset diabetes mellitus and 54 without new-onset diabetes mellitus; 169 healthy individuals with no clinical evidence of diabetes mellitus were selected as a control group. The multiplex polymerase chain reaction technique was used for genotyping GSTM1 and GSTT1 genes, using the cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene as an internal control. The genotype of GSTP1 was determined using the restriction fragment length polymorphism-polymerase chain reaction technique. Results: The frequency of both GSTM1 null and GSTT1 null genotypes was not significantly different in liver transplant patients with new-onset diabetes mellitus compared with the control group (P = .11 for GSTM1; P = .71 for GSTT1). Also, there was no statistically significant association between the frequency of the GSTP1 genotypes in the liver transplant patients with new-onset diabetes mellitus compared with controls. Neither GSTM1 nor GSTT1 null genotypes were associated with the risk of developing new-onset diabetes mellitus (P = .22 for GSTM1; P = .56 for GSTT1). However, the frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism in patients with new-onset diabetes mellitus was significantly higher than in patients without new- onset diabetes mellitus (55.8% vs 7.4%; P= .00). Thus, the risk of developing new-onset diabetes mellitus was significantly higher in patients presenting with heterozygous GSTP1 genotypes (odds ratio = 15.76; 95% confidence interval = 4.53-60.28; P = .00). Conclusions: The GSTP1 AG genotype was associated with an increased susceptibility to the development of new-onset diabetes mellitus after liver transplant.