SLC22A1-ABCB1 Haplotype Profiles Predict Imatinib Pharmacokinetics in Asian Patients with Chronic Myeloid Leukemia

Singh, Onkar; Chan, Jason Yongsheng; Lin, Keegan; Heng, Charles Chuah Thuan; Chowbay, Balram

doi:10.1371/journal.pone.0051771

Cited by 45 publications

(33 citation statements)

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“…According to the literature retrieval strategies and inclusion criteria, seven case-control studies regarding the association between the MDR1 C1236T polymorphism and leukemia risk were included in the present meta-analysis, including 846 leukemia cases and 1,523 controls in total (21)(22)(23)(24)(25)(26)(27). The countries in which these studies were conducted include China, Singapore, Sweden, Brazil and USA.…”

Section: Resultsmentioning

confidence: 99%

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Multidrug resistance gene 1 C1236T polymorphism and susceptibility to leukemia: A meta-analysis

Liu

Ruan

et al. 2014

Biomedical Reports

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Abstract. Several studies have investigated the association between multidrug resistance gene (MDR1) C1236T polymorphism and leukemia risk, however, these published studies have yielded conflicting results. Thus, the present study carried out a meta-analysis to provide a more precise estimate of the effect of this polymorphism on the susceptibility to leukemia. The published case-control studies regarding the association between MDR1 C1236T polymorphism and leukemia risk were included following a computerized search of PubMed, Elsevier, The Cochrane Library, China National Knowledge Infrastructure and Wanfang Database. Either fixed-or random-effects models were applied to calculate the combined odds ratios (ORs) and 95% confidence intervals (CIs) by RevMan 5.2 software. Seven studies, including 846 cases and 1,523 controls, were included in the present meta-analysis. The results indicated that there was no significant association between the MDR1 C1236T polymorphism and leukemia risk in overall comparisons in all four genetic models (CT vs. CC: OR, 1.31, 95% CI, 0.89-1.91, P= 0.17; TT vs. CC: OR, 2.16, 95% CI, 0.99-4.70, P= 0.05; TT vs. CC+CT: OR, 1.72, 95% CI, 0.91-3.25, P= 0.09; and CT+TT vs. CC: OR, 1.57, 95% CI, 0.96-2.56, P= 0.07). In the subgroup analysis according to specific ethnicity, age and the type of leukemia, a significant association was found in adult leukemia (CT+TT vs. CC: OR, 2.77, 95% CI, 1.05-7.31, P=0.04) and chronic myeloid leukemia (CT vs. CC: OR, 1.71, 95% CI, 1.05-2.80, P=0.03). No significant publication bias was detected by funnel plot. Therefore, the meta-analysis indicated that the MDR1 C1236T polymorphism may contribute to the susceptibility to adult leukemia and chronic myeloid leukemia. Furthe well-designed studies based on larger sample sizes are required to validate these findings. IntroductionLeukemia is a malignant clonal disorder of the hematopoietic system with extreme heterogeneity and bad prognosis. In recent years, the incidence of leukemia increased gradually (1), however, the exact biological mechanisms of leukemia have not been fully clarified (2). Epidemiological and case-control studies have found that significant environmental exposures contribute to the pathogenesis of leukemia (3). In addition, previous candidate gene association approaches and genome-wide association studies have identified the presence of inherited genetic susceptibility to this disease (4-7). Therefore, it is generally considered that the causation is multifactorial and that the interaction between exogenous or endogenous exposures and genetic susceptibility plays an important role in the etiology of leukemia (2).The human multidrug resistance gene (MDR1 or ABCB1) locates at 7q21.1 and its cDNA spans ~4.5 kb. MDR1 encodes a 170-kDa membrane transport protein called P-glycoprotein (P-gp), belonging to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily of transporters (8). P-gp functions as an ATP-dependent efflux pump and is responsible for the efflux of a variety of lipophilic...

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Section: Resultsmentioning

confidence: 99%

“…The countries in which these studies were conducted include China, Singapore, Sweden, Brazil and USA. Among these studies, there were four studies of an Asian population (22,24,25,27), two studies of a Caucasian population (21,23) and one study of a mixed population (26). All the cases had a pathologically confirmed diagnosis of leukemia.…”

Section: Resultsmentioning

confidence: 99%

Multidrug resistance gene 1 C1236T polymorphism and susceptibility to leukemia: A meta-analysis

Liu

Ruan

et al. 2014

Biomedical Reports

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“…Data on Asian population remains limited especially that in Indians. The Asian population supposedly harbours specific polymorphisms that affect sensitivity to TKI [30]. The disease also presents itself at a younger age than in western countries [31].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era—experience from a tertiary oncology centre in Southern India

Kuntegowdanahalli

Kanakasetty

Thanky

et al. 2016

ecancer

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Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.

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“…Both of these SNPs rs12208357 and rs72552763 have been linked to decreased uptake in European-American population [26]. However, their expression was not observed in Asian population [30]. Mainly expressed in liver, low-level expression of this transporter has been reported in other tissues such as kidney, brain, placenta, heart, lung, skeletal muscle [31,32].…”

Section: Discussionmentioning

confidence: 99%

OCT1 Genetic Variants are Associated with Postoperative Morphine-Related Adverse Effects in Children

et al. 2017

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Aim: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African–American (AA) children. The aim of this study is to identify the association between common OCT1 genotypes affecting morphine’s PK and clinically important postoperative morphine-related adverse outcomes. Methods: After obtaining institutional review board (IRB) approval and informed consents, 311 children ages 6–15 years, American Society of Anesthesiologists’ physical status 1 or 2 scheduled for tonsillectomy who received standard anesthetic, surgical and postoperative care were recruited. Clinical data collected included postoperative pain scores, total opioid use, incidence of PONV and RD. Four nonsynonymous SNPs of the OCT1 gene (rs12208357, rs34130495, rs72552763 and rs34059508) in each patient were genotyped using commercially available TaqMan assays. We investigated the genetic association of OCT1 with incidences of postoperative RD and PONV. Results: Caucasian and AA children differed significantly in the incidence of obstructive sleep apnea (p < 0.001) and total morphine use (p = 0.028). There were incidences of prolonged post anesthesia care unit stay in 7% of Caucasian children, while no such incidences were observed for AA children (p = 0.05). OCT1 polymorphism rs12208357 was associated with high incidences of PONV and PONV leading to prolonged post anesthesia care unit stay (p < 0.05). A significant association was also found between rs72552763 GAT deletion and high incidence of RD (p = 0.007). Conclusion: Children with certain OCT1 genotypes are associated with higher risk for RD and PONV following morphine administration leading to prolonged hospital stay. The OCT1 transporters’ effects on morphine’s PK could explain this association.

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SLC22A1-ABCB1 Haplotype Profiles Predict Imatinib Pharmacokinetics in Asian Patients with Chronic Myeloid Leukemia

Cited by 45 publications

References 50 publications

Multidrug resistance gene 1 C1236T polymorphism and susceptibility to leukemia: A meta-analysis

Multidrug resistance gene 1 C1236T polymorphism and susceptibility to leukemia: A meta-analysis

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era—experience from a tertiary oncology centre in Southern India

OCT1 Genetic Variants are Associated with Postoperative Morphine-Related Adverse Effects in Children

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