OP0025 Genetic association of C480G polymorphism of SLC22A1 with clinical resistance to imatinib mesylate in Malaysian patients with chronic myeloid leukaemia
Background Despite imatinib mesylate (IM) being the gold standard drug for treatment of chronic myeloid leukaemia (CML), a significant proportion of CML patients develop IM resistance due to a heterogeneous array of mechanisms. IM uptake is mediated by human organic cation transporter 1 protein enco...
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| Published in: | European journal of cancer (1990) Vol. 50; p. e9 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Ltd
01-05-2014
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Background Despite imatinib mesylate (IM) being the gold standard drug for treatment of chronic myeloid leukaemia (CML), a significant proportion of CML patients develop IM resistance due to a heterogeneous array of mechanisms. IM uptake is mediated by human organic cation transporter 1 protein encoded by the solute carrier protein 22 gene ( SLC22A1 ). Genetic variants in transporters cause population-specific differences in drug transport and are responsible for considerable interindividual variation in pharmacotherapy. Genetic polymorphisms in SLC22A1 might affect IM response. We investigated whether a SLC22A1 polymorphism, C480G (rs683369), which leads to Leu160Phe replacement, is associated with IM response in Malaysian patients with CML. Methods In total, 110 CML patients (55 IM good response and 55 IM resistant) who had been administered 400 mg IM daily for at least 18 months were genotyped for rs683369 polymorphism using the PCR-RFLP method. Genotypes were categorised into homozygous wild type, heterozygous, and homozygous variant. The genotype and allele frequencies between the two groups were compared and the risk association was established with logistic regression analysis. Findings Significant differences in genotype ( p < 0.001) and allele frequencies ( p < 0.002) were observed between the two groups. The risk of developing resistance was significantly higher for CML patients with CG genotype (odds ratio [OR] 4.962, 95% confidence interval [CI] 2.006–12.471, p < 0.001) and insignificantly higher for CML patients with GG genotype (OR 6.316, 95% CI 0.523–109.091, p = 0.083). Interpretation Genetic variation C → G might be leading to a decrease in enzymatic activity that results in an inadequate response to treatment. Carriers of the G allele of SLC22A1 , C480G, might be at increased risk of acquiring resistance. Focusing on the genetic background of the host might be important for a comprehensive assessment of the prognosis of CML therapy. Research supported by Research University Grants, Universiti Sains Malaysia (No: 1001/PPSP/812103). |
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| ISSN: | 0959-8049 1879-0852 |
| DOI: | 10.1016/j.ejca.2014.03.043 |