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

https://doi.org/10.19106/JMedSci005001201806

Sunarto Ang(1*), Akhmad Kharis Nugroho(2), Ahmad Hamim Sadewa(3), Lukman Hakim(4), . Mustofa(5)

(1) Department of Internal Medicine, Abdul Wahab Sjahranie General Hospital, Samarinda, East Kalimantan
(2) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
(3) Department of Biochemistry, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(4) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
(5) Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Rifampin is one of first-line drugs for the treatment of tuberculosis. In Indonesia nearly all
tuberculosis patients show lower rifampin plasma concentrations 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 Abdul
Wahab Sjahranie General 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. 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.


Keywords


SLCO1B1*15 haplotype; rifampin; tuberculosis; clinical outcome

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References

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DOI: https://doi.org/10.19106/JMedSci005001201806

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