Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia

Abstract

Objectives: The N-Acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in xenobiotic metabolism, which contributes to the detoxification of numerous cancer therapy-induced products. However, the NAT2 genotype/phenotype is not fully understood and few studies have reported its relationship with CML. The aim of this study was to determine whether its polymorphisms ( C481T, G590A, 803A>G and 857G>A ) have a role in chronic myeloid leukemia susceptibility (CML) in Sudanese population. Methods: We performed a case- control study. DNA from 200 CML patients and 100 controls was analyzed for the NAT2 polymorphisms using PCR-RFLP assay. Results: The study showed NAT2 polymorphisms 803AG are associated with CML protection by a factor of 2.3, (OR = 0.044, 95% CI: 0.020-0.095, p = 0. 000). The study indicated that the heterozygous (GA) and mutant (AA) variants of the G857A genotype also offer protection, (OR = 0.002, 95% CI: 0.002-0.019, p = 0. 000) and (OR = 0.018, 95% CI: 0.002-0.133, p = 0. 000), respectively. Conclusion: There was no significant difference in CML diagnosis among Sudanese cases with the 481C→T and 590G→A polymorphisms. But patients with the compound NAT2 genotypes 481CT/803 AG, 590AG/ 803AG, 590AG/ 803GG, 590AA/ 803AG and 590GG/ 803AG were found to have a reduced risk. The current study demonstrates that polymorphisms of NAT2 A803G and G857A might also act as protective factors against developing the disease.

BCR-ABL Kinase Domain mutations - E255K, Y253 H and M351T among Sudanese population with CML

“…and in turn reduce the mortality rate of the disease. For this reason, recent studies have been instigated in Sudan regarding CML patients, to ascertain how susceptibility to the disease is affected by polymorphism of certain genes such as xenobiotic ones [4][5][6] and BCR-ABL kinase gene as in this study. The Ph (Philadelphia) chromosome is considered a cytogenetic hallmark of CML, as it occurs in 90-95% of patients [7].…”

Impact of Methionine Synthase Reductase Polymorphisms in Chronic Myeloid Leukemia Patients

“…Few other studies have also examined the relationship between MTRR 66 AG polymorphism and cancer risk. These studies found a significant association between a decreased risk of acute lymphoblastic leukemia and an augmented risk for hepatocellular carcinoma [ 32 , 33 , 34 , 35 , 36 ]…”

Genetic Polymorphisms of Xenobiotics-Metabolizing Enzymes Contributing to Leukemia

“…In this case, chromosomal translocation results in an oncogenic BCR-ABL gene fusion that increases tyrosine kinase (TK) activity. Kinases that are abnormally activated disrupt downstream signaling pathways, resulting in abnormal cell proliferation, differentiation, and resistance to cell Genetic Polymorphisms of Xenobiotics-Metabolizing Enzymes Contributing to Leukemia DOI: http://dx.doi.org/10.5772/intechopen.107324 death [43]. Joshi et al reported the CYP2C19 gene polymorphisms in susceptibility to CML.…”

“…A meta-analysis by Jiang et al investigated the relationship between NAT2 polymorphisms and onset risk of acute leukemia and reported there is no significant difference found between the fast-acetylator incidence of NAT2 haplotype and the onset risk of acute lymphoblastic leukemia (ALL, OR = 0.70, 95% CI = 0.45-1.08) or AML, OR = 0.79, 95% CI = 0.46-1.47) [52]. No significant difference was found in NAT2 fast and slow acetylator frequencies between CML patients and controls [47], while Tebien et al revealed the protective effect of NAT2A 803G and G857A against CML [43].…”