CYP3A5*3, CYP3A4*18 AND CYP2B6*6 GENOTYPES AND CHRONIC MYELOID LEUKEMIA DEVELOPMENT IN AZERBAIJAN
2023
Karimova, Nigar | Asadov, Chingiz | Hasanova, Aypara | Bayramov, Bayram | Shirinova, Ayten | Alimirzoyeva, Zohra
The management of chronic myeloid leukemia (CML) has been dramatically improved in recent years. The cytochromes P450 (CYP) family is a major drug-metabolizing enzyme complex coordinating most currently prescribed drugs. Thus, single nucleotide polymorphisms (SNPs) in these enzyme coding genes may negatively affect drugs biotransformation and xenobiotics detoxification. The given experiment aimed to assess the influence of common CYP SNPs on susceptibility to CML. The genotyping of 153 CML patients and 100 healthy sex and age-matched controls were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. To validate the obtained results, samples were sequenced via next-generation sequencing. The frequencies of homozygous mutant genotype (GG) and mutant G (*3) allele of CYP3A5*3 were significantly elevated in subjects compared to the control group; differences were statistically significant (p<0.05). In this study, no association was found between CYP3A4*18 and CML susceptibility. Although CML patients carrying GT and TT genotypes and T allele were associated with a significantly higher risk of chronic myeloid leukemia (OR 1.2019; 95% CI: 0.6921–2.0873, OR 1.8919 95% CI: 0.8405–4.2587 and OR 1.3573;95% CI: 0.9188–2.0053, respectively), the association was not statically significant. We found that the abundantly present polymorphism of CYP3A5*3 is associated with susceptibility to develop CML, which raises suggestions of its role as a genetic marker of the risk to deliver CML.
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