Evaluation of genetic polymorphisms of N-acetyltransferase 2 and relation with chronic myeloid leukemia

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. We performed a case- control study to determine whether its polymorphisms (C481T, G590A, 803A>G and857G>A) have a role in chronic myeloid leukemia susceptibility (CML) in Sudanese population. 

Methods: DNA from 200 CML patients and 100 controls was analyzed for the NAT2 polymorphisms using PCR-RFLP assay. 

Results: It is known that NAT2 polymorphisms 803AG are associated with CML protection by a factor of 2.3, (OR = 0.44, 95% CI: 0.020-0.095, p = 0. 000). It is also known 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/ 2803AA 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.