scholarly journals SLCO1B1 Gene

2020 ◽  
Author(s):  
Keyword(s):  
Slco1b1 Gene

scholarly journals Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy

2009 ◽  
Vol 9 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Tomomi Furihata ◽  
Naoki Satoh ◽  
Tomoharu Ohishi ◽  
Miyuki Ugajin ◽  
Yoshio Kameyama ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Japanese Patient ◽  
Slco1b1 Gene

scholarly journals The role of vitamin D and SLCO1B1 gene polymorphism in statin-associated myalgias

2010 ◽  
Vol 2 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Randy Linde ◽  
Lihong Peng ◽  
Manisha Desai ◽  
David Feldman
Keyword(s):  
Vitamin D ◽  
Gene Polymorphism ◽  
Slco1b1 Gene

Pharmacogenetics of SLCO1B1 gene and the impact of *1b and *15 haplotypes on irinotecan disposition in Asian cancer patients

2006 ◽  
Vol 16 (9) ◽  
pp. 683-691 ◽  
Author(s):  
Xiaoqiang Xiang ◽  
Srinivasa Rao Jada ◽  
Hui Hua Li ◽  
Lu Fan ◽  
Lai San Tham ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Slco1b1 Gene ◽  
The Impact

The impact of the SLCO1B1 gene polymorphism on the lipid-lowering effect of pitavastatin

2009 ◽  
Vol 137 ◽  
pp. S103-S104
Author(s):  
H. YUAN ◽  
X. LU ◽  
Z.J. HUANG ◽  
B. TANG ◽  
G.P. YANG
Keyword(s):  
Gene Polymorphism ◽  
Lipid Lowering ◽  
Lowering Effect ◽  
Slco1b1 Gene ◽  
The Impact ◽  
Lipid Lowering Effect

SLCO1B1 gene variability influences lipid-lowering efficacy on simvastatin therapy in Southern Brazilians

2012 ◽  
Vol 50 (3) ◽  
Author(s):  
Vinicius A. Sortica ◽  
Marilu Fiegenbaum ◽  
Luciana O. Lima ◽  
Cézar R. Van der Sand ◽  
Luis C. Van der Sand ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Simvastatin Therapy ◽  
Slco1b1 Gene ◽  
Gene Variability

Non-synonymous polymorphisms in the human SLCO1B1 gene: an in vitro analysis of SNP c.1929A>C

2007 ◽  
Vol 279 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Annick Seithel ◽  
Kathrin Klein ◽  
Ulrich M. Zanger ◽  
Martin F. Fromm ◽  
Jörg König
Keyword(s):  
Slco1b1 Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis

Predictors of Delayed Clearance and Toxicities from High Dose Methotrexate in Patients Receiving Hypercvad Regimen for Treatment of Lymphoid Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1630-1630
Author(s):  
Hong Yen Ng ◽  
Pei Shi Ong ◽  
Xue Ming Loy ◽  
Yufei Chen ◽  
Yeow Tee Goh
Keyword(s):  
Sample Size ◽  
Small Sample ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Toxicity Profile ◽  
Clinical Factors ◽  
Lymphoid Malignancies ◽  
Dose Methotrexate ◽  
Slco1b1 Gene ◽  
Number Of Treatment

Abstract Introduction: High dose Methotrexate (HDMTX) has been the backbone of chemotherapeutic regimens used for the treatment of lymphoid malignancies. Altered disposition of MTX may result in increased systemic exposure accompanied by severe adverse effects and organ toxicities. Diversity in toxicity profile has been shown to be associated with various clinical factors as well as genetic polymorphisms. In particular, single nucleotide polymorphisms (SNPs) in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene especially rs4149056 and rs2306283 had been previously reported to be significantly associated with MTX concentration at 24 hours post-infusion, MTX AUC from 0-48 hours, MTX clearance and toxicities in the Caucasian pediatric population. Aim: This study aimed to characterize clearance and toxicity profile [in particular acute kidney injury (AKI) and hepatotoxicity]; and identify clinical and genetic covariates associated with clearance and toxicities of HDMTX in patients receiving HyperCVAD-B regimen for treatment of lymphoid malignancies in the local setting. Methods: This single-centered, retrospective study included all treatment-naïve patients of Asian descent who received HDMTX as part of the HyperCVAD-B regimen for treatment of lymphoid malignancies from January 2008 to December 2015 in Department of Hematology, Singapore General Hospital. Pertinent clinical data including baseline demographics, disease characteristics, treatment details, plasma MTX levels, and treatment outcomes were extracted from case notes and electronic records onto a standardized data collection form. Association between toxicities parameters and MTX levels were analyzed. Genotyping for two SNPs in the SLCO1B1 gene namely, rs2306283 and rs4146056 was using blood samples obtained from the Hematology Department Tissue Repository. Primary endpoint was incidence of delayed clearance and toxicities of HDMTX in the study population. Secondary endpoints included clinical factors and genetic covariates associated with reduced MTX clearance and toxicities. Results: A total of 102 patients (215 treatment cycles) were included, with each patient receiving median of 2 cycles (range, 1 to 6). Median age was 45 years (range, 18 - 69), and 58 (56.9%) were male. Eighty-seven patients were diagnosed with acute lymphoblastic leukemia (ALL), whereas 12 patients had lymphoma. Sixty-one patients (59.8%) were found to have at least 1 episode of delayed clearance, occurring in 89 (41.4%) treatment cycles. Median time to MTX clearance was significantly longer in patients with delayed clearance at 69.8 hours (range, 4.5-277.2) as compared to 41 hours (range, 0 - 86.3 hours), p<0.001. Approximately 25% and 47% of the patients developed AKI and hepatotoxicity attributable to MTX, respectively. A significant association between delayed clearance and occurrence of AKI was observed, with 24% of patients with delayed clearance developing AKI vs 2% in those without delayed clearance, p<0.001. Number of treatment cycles [odds ratio (OR) = 2, 95% confidence interval (CI) 1.3 - 3.1, p = 0.002]; and age ≥ 40 (OR 3.7, 95% CI 1.4 - 9.6, p = 0.008) were found to be associated with delayed clearance. Occurrence of delayed clearance (OR = 29, 95% CI = 3.7 - 228, p = 0.001), and baseline hepatic impairment (OR = 9.5, 95% CI = 2 - 45, p = 0.005) were found to predict for AKI and hepatotoxicity, respectively. Genotyping for SLCO1B1 rs2306283 and rs4146056 was carried out for 39 patients with samples available in the repository. Frequencies and outcomes were shown in Table 1 and Table 2, respectively. Due to the small sample size, no definitive correlations between specific genotypes and clearance and outcomes could be elucidated. Conclusion: Delayed clearance of HDMTX occurred in a substantial proportion of patients at approximately 60%, which was in turn associated with occurrence of AKI. Risk of delayed clearance seemed to increase with age (≥ 40) and number of treatment cycles. This underscores the need for more effective strategies to facilitate clearance of HDMTX especially in patients with identified risk factors. Larger sample size would be essential to determine associations between genotypes and clearance and toxicities. Disclosures No relevant conflicts of interest to declare.

SLCO1B1 Gene Variants and Urine Arsenic Metabolites in the Strong Heart Family Study

2013 ◽  
Vol 2013 (1) ◽  
pp. 4250
Author(s):  
Matthew O. Gribble ◽  
V. Saroja Voruganti ◽  
Cheryl D. Cropp ◽  
Kevin A. Francesconi ◽  
Walter Goessler ◽  
...  
Keyword(s):  
Family Study ◽  
Gene Variants ◽  
Slco1b1 Gene ◽  
Arsenic Metabolites ◽  
Strong Heart Family Study

scholarly journals MTHFR and SLCO1B1 Gene Polymorphism and Methotrexate Induced Toxicity in Children with Acute Lymphoblastic Leukemia in the Northwest of Mexico

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4359-4359
Author(s):  
Samantha Fierro Sáenz ◽  
Claudia Selene Portillo Zavala ◽  
Veronica Moreno Brito ◽  
Joel Dominguez Viveros ◽  
Everardo González Rodríguez
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Real Time ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Mthfr Gene ◽  
High Dose ◽  
Real Time System ◽  
Exact Test ◽  
Logistic Regressions ◽  
Slco1b1 Gene

Abstract Introduction. Acute lymphoblastic leukemia (ALL) represents approximately 52% of pediatric cancer diagnoses in Mexico and is the leading cause of death by disease among children of 5 to 14 years. The use of pharmacogenomics for the detection of germline genetic variations, which are associated with sensitivity or toxicity to chemotherapy, is one of the recent strategies to improve survival. Some mutations present in genes related to the metabolism or transport of methotrexate (MTX) have been associated with the occurrence of toxicities during treatment in pediatric acute lymphoblastic leukemia. The effect of the SNP´s rs1801131, rs1901133 in the MTHFR and rs4149058, rs4149081 in the SLCO1B1 gene have not been studied in Northwest Mexican children with acute lymphoblastic leukemia. Patients and methods. Eligible patients were infants less than 1 year to adolescents less than 18 years of age, diagnosed with B-ALL at the Specialties Children's Hospital of Chihuahua, Mexico. Patients were treated according to the locally protocols based on the St. Jude Children's Research Hospital Total XIIIB and Total XV protocols. We followed-up for two to four weeks after 24 hours high dose MTX (1 to 5 g/m 2) administration. Toxicity data were collected objectively from the patient's medical files and adverse effects were classified as a dichotomous variable yes/no. Genomic DNA was extracted with the Master Pure DNA purification kit (Epicentre Illumina® Company) from peripheral blood. Genotyping assays were performed by real-time polymerase chain reaction, using rhAMp® IDT® genotyping probes (Iowa, USA) and Quant Studio 3 Applied Biosystems Real-Time System Thermal Cycler (Thermo Fisher Scientific®). For statistical analysis association between MTX dose, presence of toxicity, and genetic polymorphisms was evaluated by the chi-square or Fisher's exact test. The effect sizes of the associations were estimated by the OR's from univariate logistic regressions and multivariate logistic regressions to account for the possible confounding effect of sex and age. Analyses were performed by using SAS System and IBM SPSS Statistics Base 22.0 software. Results. The study population demographics and clinical characteristics are summarized in Table 1. MTHFR and SLCO1B1 genotype in our patients and controls obtained from the 1000 Genomes Project database are shown in table 2. In general, a predominance of toxicity events is observed in patients heterozygous for both polymorphisms in the MTHFR gene, but not in the SLCO1B1 gene (Figure 1). Through a logistic regression analysis, we observed an association of 8% between the polymorphisms rs1801131, rs1901133, rs4149058, rs4149081 and the presence of anemia. The AC heterozygous of the rs1801131 has the strongest association with a positive coefficient (+1.1355) and when comparing AC heterozygotes with CC mutated homozygotes, an Odds Ratio (OR) of 4.64 (CI: 95%, 0.719) was observed, identifying it as a risk factor. In contrast, the homozygous AA of the same gene, presented a negative coefficient (-0.7354), thus decreasing the probability of presenting anemia in this population. The presence of neutropenia was associated in 25% with the polymorphisms rs1801131, rs1901133, rs4149058, rs4149081. The AA homozygous of rs1801131 decreased the probability of developing neutropenia (coefficient -0.7643, p=0.04) and the TC heterozygous of rs4149056 increased the probability when comparing with the wild TT homozygotes (OR of 2.91, CI: 95%, 0.496). Liver enzymes elevation was associated in 84% with the polymorphisms rs1801131, rs1901133, rs4149058, rs4149081. We found that the presence of TC heterozygote of rs4149056 decreased the probability of hepatotoxicity (coefficient -1.5718, p=0.03) and GA heterozygote of rs41419081 increased it (coefficient +3.2056, p=0.004) (Table 3). According to this statistical model, we could not analyze the association between the polymorphisms rs1801131, rs1901133, rs4149058, rs4149081 and thrombocytopenia, mucositis, febrile neutropenia or creatinine elevation. Conclusion Toxicity related to treatment is one of the most important causes of death among pediatric ALL patients in Mexico, the development of precision medicine through the identification of SNPs associated with the variability in our patients' response is an alternative to minimize methotrexate toxicity and maximize its benefit during its use. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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