&lt;I&gt;SLCO1B1&lt;/I&gt; gene polymorphisms do not influence plasma rifampicin concentrations in a South Indian population

Ramesh, K; Kumar, Ashok; Thiruvengadam, Kannan; Vijayalakshmi, R.; Sudha, Vasudevan; Nesakumar, S Manohar; Bharathiraja, T; Jayabal, Lavanya; Swaminathan, Sowmya; Ramachandran, Geetha

doi:10.5588/ijtld.15.1007

Cited by 21 publications

(25 citation statements)

References 13 publications

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“…Much interest in Europe has focused on the role of rs4149056 (521T>C, *5) in toxicity of statin therapy (27), while studies in South Africa and Uganda have implicated two SLCO1B1 SNPs (rs4149032 and rs11045819) in reduced RIF exposure (18–20). However, in keeping with a recent report from southern India (21), inclusion of these genotypes did not significantly improve the PK model fit for RIF in our study.…”

Section: Discussionsupporting

confidence: 86%

“…In addition, while rs11045819 is believed to be functional (463C>A, *4), rs4149032 is an intronic SNP of unclear functional status which, in European populations, is in strong linkage disequilibrium with rs11045819 (28). However, these SNPs had a low level of linkage disequilibrium (D′ 0.16) in Malawi, echoing findings from South Africa (18) and southern India (21). There are large differences in linkage disequilibrium worldwide and within Africa (15), so it is possible that previously recognized SNPs may tag functional genes in some populations but not others.…”

Section: Discussionsupporting

confidence: 52%

“…Reports from South Africa and Uganda suggested that two SLCO1B1 single nucleotide polymorphisms (SNPs), rs11045819 and rs4149032, are common in African patients and associated with reduced RIF plasma exposure (18–20). However, a recent study from a TB-endemic population in southern India reported lower variant allele frequency of these SNPs than the prior African work and no genotypic effect on the pharmacokinetics of RIF (21). More data from a broader range of global settings are required to assess the effect of SLCO1B1 genetics on rifampin exposure.…”

Section: Introductionmentioning

confidence: 76%

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Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis

Sloan

McCallum

Schipani

et al. 2017

Antimicrob Agents Chemother

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Variable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC and CES-1) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2, using a two-stage strategy to improve information during the absorption phase. In contrast to recent studies in South Africa and Uganda, SNPs in SLCO1B1 did not explain variability in AUC0–∞ of rifampin. No pharmacokinetic associations were identified with AADAC or CES-1 SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampin exposure may vary between African populations. SLCO1B1 and other novel candidate genes, as well as nongenetic sources of interindividual variability, should be further explored in geographically diverse, adequately powered cohorts.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 76%

See 1 more Smart Citation

Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis

Sloan

McCallum

Schipani

et al. 2017

Antimicrob Agents Chemother

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“…We undertook substudies in the same population to examine the influence of polymorphisms in the NAT2 and SLCO genes on plasma INH and RMP concentrations, respectively. While the NAT2 genotypes significantly impacted INH levels, the SLCO genotypes (rs11045819, rs4149032, and rs4149033) did not influence RMP concentrations (18,19). In this study, we undertook NAT2 genotyping in only about a third of the patients.…”

Section: Discussionmentioning

confidence: 99%

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India

Ramachandran

Kupparam

Chandrasekaran

et al. 2017

Antimicrob Agents Chemother

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The Indian Revised National Tuberculosis (TB) Control Programme uses thrice-weekly treatment with standard drug dosages. The role of plasma drug levels and other factors in determining TB treatment outcomes is not well understood. We aimed to determine the factors influencing the concentrations of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) at 2 h postdosing in adult TB patients and to study the factors impacting TB treatment outcome. We recruited 1,912 adult TB patients (newly treated and retreated patients) with pulmonary/extrapulmonary TB receiving antitubercular treatment (ATT) in the RNTCP in Chennai, India. At steady state, the concentrations of RMP, INH, and PZA were determined at 2 h postdosing after supervised drug administration. A total of 1,648 patients had a favorable outcome, while 264 (14%) had an unfavorable outcome. A total of 91%, 16%, and 17% of the patients had suboptimal concentrations of RMP (Ͻ8 g/ml), INH (Ͻ3 g/ml), and PZA (Ͻ20 g/ml), respectively. Factors associated with treatment outcome were low RMP concentrations (adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.89 to 0.99; P ϭ 0.036), category II ATT (aOR, 2.39; 95% CI, 1.56 to 3.65; P Ͻ 0.001), low body weight (aOR, 0.96; 95% CI, 0.94 to 0.98; P Ͻ 0.001), alcohol use (aOR, 2.17; 95% CI, 1.42 to 3.31; P Ͻ 0.001), male gender (aOR, 1.92; 95% CI, 1.02 to 3.62; P ϭ 0.043), and baseline INH resistance (aOR, 5.74; 95% CI, 3.12 to 10.59; P Ͻ 0.001), which significantly increased the likelihood of an unfavorable outcome in multivariate logistic regression analysis. Further studies are needed to optimize anti-TB drug dosages and improve cure rates. Drug susceptibility testing at the baseline and attention to undernutrition and alcohol dependence are other important interventions.

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“…Other recent studies showed that it did not influence the exposure and involves genetic variability 11,12 while presently there are no studies of the major SNPs in Indonesian patients. This study aimed to determine the major SNPs which may influence efficacy of treatment among Indonesian PTB and EPTB patients and the second objective of the study was to evaluate their potential impact on the clinical outcome.…”

Section: C463amentioning

confidence: 99%

The SLCO1B1*15 haplotype associated with lower clinical outcome in Indonesian tuberculosis patients

Ang¹,

Nugroho²,

Sadewa³

et al. 2018

JMedScie

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Rifampin is one of first-line drugs for the treatment of tuberculosis. In Indonesia nearly all tuberculosis patients show lower rifampin plasma concentration's possibly due to genetics. Rifampin is a substrate of the organic anion-transporting polypeptide 1B1 (OATP 1B1) encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1). This study aimed to identify haplotype polymorphisms of tuberculosis drug transporters with an impact on clinical outcome in tuberculosis patients. Thirty-six patients from I.A Moeis District Hospital, Samarinda, East Kalimantan were involved in the study. Buffy coat from patient blood samples were tested for SLCO1B1 and SLCO1B3 polymorphisms by RFLP and ARMS PCR, whereas the clinical outcome was examined based on the sputum conversion histopathology residuals. The frequency of patients with SLCO1B1*15 haplotype was 63.9%. The SLCO1B1*15 haplotype was associated with susceptibility to failure of clinical outcome (p=0.005; RR=4.52; 95% CI: 1.22-16.64). The OATP1B1*15 haplotype revealed that the failure of clinical outcome was markedly increased compared to the three other haplotypes. These results suggest that the SLCO1B1*15 haplotype is an important predisposing factor for lower clinical outcome. Our data indicate that individualized treatment should be considered for Indonesian tuberculosis patients based on genetics characteristics of patients.

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<I>SLCO1B1</I> gene polymorphisms do not influence plasma rifampicin concentrations in a South Indian population

Abstract: This is the first study to show that rs11045819, rs4149032 and rs4149033 polymorphisms in the SLCO1B1 gene did not influence RMP concentrations in Indian patients.

Cited by 21 publications

References 13 publications

Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis

Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis

Factors Influencing Tuberculosis Treatment Outcome in Adult Patients Treated with Thrice-Weekly Regimens in India

The SLCO1B1*15 haplotype associated with lower clinical outcome in Indonesian tuberculosis patients

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