Genetic Polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and Susceptibility to Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Chinese Population-Based Prospective Case–Control Study

Sun, Qin; Liu, Haipeng; Zheng, Ruijuan; Wang, Peng; Liu, Zhibin; Wang, Sha; Xiao, Heping

doi:10.1007/s40261-017-0572-6

Cited by 29 publications

(32 citation statements)

References 29 publications

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“…Elevated ALT levels might indicate a higher risk of hepatotoxicity [ 30 ]. It was reported that SLCO1B1 genetic variants are associated with drug-induced hepatotoxicity [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes

Alhawari

Jarrar

AlKhatib

et al. 2020

Life

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Atorvastatin is commonly used among type 2 diabetic (DM2) patients at the University of Jordan Hospital to prevent cardiovascular complication. However, we noticed that there is a wide inter-individual variation in the efficacy and toxicity of atorvastatin. This study aimed to find out the effects of major genetic variants in 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Apolipoprotein E (APOE), and Solute Carrier Organic Anion (SLCO1B1) genes on atorvastatin response among DM2 patients. A sample of 139 DM2 patients on 20 mg of atorvastatin was included in this study. The lipid and glycemic profile and the levels of hepatic enzymes alanine aminotransferase (ALT) and aspartate transaminase were recorded before and after 3 months of atorvastatin treatment. Additionally, the genetic variants HMGCR rs17244841,APOE rs7412 and rs429357, and SLCO1B1 rs2306283 and rs11045818 were genotyped using an Applied Biosystems DNA sequencing method (ABI3730×1). We found that atorvastatin reduced total cholesterol and low-density lipoprotein (LDL) more significantly (p-value < 0.05) in patients with wild genotype than variant alleles APOE rs7412C > T and SLCO1B1 rs2306283A > G. Furthermore, the ALT level was elevated significantly (p-value < 0.05) by 27% in patients with heterozygous SLCO1B1 rs11045818 G/A genotype, while it was not elevated among wild genotype carriers. Additionally, atorvastatin reduced total cholesterol more significantly (p-value < 0.05) in patients with SLCO1B1 rs2306283A and rs11045818G haplotypes and increased ALT levels by 27% (p-value < 0.05) in patients with SLCO1B1 rs2306283G and rs11045818A haplotypes. In conclusion, it was found in this study that APOE rs7412, SLCO1B1 rs2306283, and rs11045818 genotypes can be considered as potential genetic biomarkers of atorvastatin response among DM2 patients of Jordanian Arabic origin. Further clinical studies with larger sample numbers are needed to confirm these findings.

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“…Elevated ALT levels might indicate a higher risk of hepatotoxicity [ 30 ]. It was reported that SLCO1B1 genetic variants are associated with drug-induced hepatotoxicity [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes

Alhawari

Jarrar

AlKhatib

et al. 2020

Life

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“…The sample size calculation of this protocol was based on studies of genetic analyses of ATDH. In previous studies, the sample sizes used have been relatively small (ranging from 846 to 46147), which makes it difficult to achieve an adequate statistical power. Furthermore, too small a sample size to detect true evidence for an association increases false negative rates and reduces the reliability of a study,48 which is one of the reasons for heterogeneity of results between different studies.…”

Section: Discussionmentioning

confidence: 99%

Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study

Yang

Pan

et al. 2019

BMJ Open

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IntroductionTuberculosis (TB) continues to be an important public health problem throughout much of the world. Drug treatment is the only effective treatment method, but adverse drug events (ADEs) and adverse drug reactions (ADRs) can affect medication adherence. As the number of drug-resistant TB patients and the number of anti-TB drugs have increased, it is necessary to explore the risk factors for ADEs/ADRs to reduce their occurrence. This study aims to build a home-based anti-TB treatment cohort and to recognise the incidences, prognosis and risk factors of anti-TB drug-induced ADEs/ADRs in real-world experiences.Methods and analysisThis study is a multicentre, prospective observational cohort study. The study population will consist of 3200 newly diagnosed TB patients between January 2019 and December 2020. After initiating the anti-TB treatment, all patients will be followed up until finishing treatment unless they withdraw, and we will record personal drug use and signs and/or symptoms of discomfort. Patients will receive scheduled laboratory tests in designated hospitals every 2 weeks during the first 2 months, and the residual blood sample after conducting the laboratory tests will be preserved. The ADEs/ADRs will be placed into eight categories: liver dysfunction, gastrointestinal reactions, drug allergy, arthralgia or muscle pain, nervous system disorders, haematological system disorders, renal impairment and others.Ethics and disseminationThis study protocol has been approved by the ethics committees of Nanjing Medical University. All patients will give written informed consent before enrollment. The findings of the study will be published in peer-reviewed journals and will be presented at national and international conferences.

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“…Organic anion‐transporting polypeptide (OATP) 1B1 is one of the most important drug transporters that mediates the hepatic uptake of many endogenous and xenobiotic compounds . OATP1B1 is encoded by gene of SLCO1B1 on chromosome 12p and expressed on the basolateral membrane of human hepatocytes . Numerous genetic variants have been identified in the SLCO1B1 gene, especially the non‐synonymous SNPs, such as rs4149056 (c.521T > C) in exon 5 and rs2306283 (c.388A > G) in exon 4, which has been found to alter the activity of OATP1B1 both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Previously, a Chinese population‐based study found that the UGT1A1*27 and UGT1A1*28 were associated with an increased risk of anti‐tuberculosis‐induced hepatotoxicity (ATDH) . In addition, Sun et al found that UGT1A1*6 (rs4148323) significantly reduced the risk of ATDH. However, in our study, we found that UGT1A1*6 (rs4148323) was associated with a significantly increased risk of MMI‐DILI before Bonferroni correction.…”

Section: Discussionmentioning

confidence: 99%

Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole‐induced liver injury

Jin

Fan

et al. 2019

Basic Clin Pharma Tox

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Methimazole (MMI) has been used in the therapy of Grave's disease (GD) since 1954, and drug‐induced liver injury (DILI) is one of the most deleterious side effects. Genetic polymorphisms of drug‐metabolizing enzymes and drug transporters have been associated with drug‐induced hepatotoxicity in many cases. The aim of this study was to investigate genetic susceptibility of the drug‐metabolizing enzymes and drug transporters to the MMI‐DILI. A total of 44 GD patients with MMI‐DILI and 118 GD patients without MMI‐DILI development were included in the study. Thirty‐three single nucleotide polymorphisms (SNPs) in twenty candidate genes were genotyped. We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI‐DILI; however, no significant difference existed after Bonferroni correction. Haplotype analysis showed that the frequency of SLCO1B1*1a (388A521T) was significantly higher in MMI‐DILI cases than that in the control group (OR = 2.21, 95% CI = 1.11‐4.39, P = 0.023), while the frequency of SLCO1B1*1b (388G521T) was significantly higher in the control group (OR = 0.52, 95% CI = 0.29‐0.93, P = 0.028). These results suggested that genetic polymorphisms of SLCO1B1 were associated with susceptibility to MMI‐DILI. The genetic polymorphism of SLCO1B1 may be important predisposing factors for MMI‐induced hepatotoxicity.

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Genetic Polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and Susceptibility to Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Chinese Population-Based Prospective Case–Control Study

Abstract: Genetic polymorphisms of SLCO1B1 and UGT1A1 were found to be associated with susceptibility to ATDH. Molecular identification of susceptibility genes provides a theoretical foundation for predicting the likelihood of ATDH and predicting treatment outcomes in tuberculosis patients.

Cited by 29 publications

References 29 publications

The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes

The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes

Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study

Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole‐induced liver injury

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