Original Research Article
Year: 2020 | Month: April-June | Volume: 5 | Issue: 2 | Pages: 69-78
Role of Human Organic Cation Transporter 1(SLC22A1) Gene Polymorphisms in Modifying Response to Imatinib in CML Patients
Namrata Bhutani1, Deepika Arora2, Neha Bhutani3
1Department of Biochemistry, Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi. India
2Department of Anaesthesia, Royal London Hospital, NHS Barts Health, London, United Kingdom
3ESIC Dental College, Rohini, New Delhi, India
Corresponding Author: Neha Bhutani
ABSTRACT
Background: Human organic cation transporter1 (hOCT1,SLC22A1), an influx transporter,is responsible for the uptake of Imatinib into chronic myeloid leukemia (CML) cells. Variation in clinical response to Imatinib has been observed with two nonsynonymous SNPs in hOCT1 gene ,namely M420del and M408V in some populations.
Aims: The study aimed to study hoct1 gene polymorphism M420del & M408V in CML patients treated with imatinib & their effect on hematological and molecular response to imatinib .Also, the synergistic effect of M408V & M420del on hematological and molecular response to imatinib were studied. Additionally, correlation of these polymorphisms with hoct1 gene expression was studied.
Methodology: Newly diagnosed CML patients, in the age group 18-80 years, with diagnosis confirmed by qualitative PCR for BCR-ABL1 fusion gene , who were to be initiated on Imatinib therapy were included in the study. Detection of BCR-ABL1 fusion gene transcripts for confirmation of diagnosis of CML by Qualitative multiplex RT-PCR ., evaluation of hOCT1 gene expression by Real Time quantitative RT-PCR (qPCR) and detection of gene polymorphism in hOCT1 gene: SNPs M420del (rs35191146) and M408V (rs628031) was done by Allele Specific PCR (AS-PCR).
Results: It was observed that patients having normal homozygous genotype for M408V and mutant homozygous or heterozygous genotype for M420del had an increased tendency towards imatinib resistance as compared to patients who had normal homozygous genotype for both the polymorphisms. On the other hand, this effect was not seen in patients with mutant homozygous or heterozygous genotypes for both polymorphisms.
Conclusions: Mutant M420del allele may be linked to poor outcome of imatinib treatment in CML, however simultaneous presence of mutant M408V allele appears to circumvent this effect.
Keywords: Human organic cation transporter1 (hOCT1,SLC22A1), gene polymorphism, CML patients, imatinib