TITLE:
SLCO1B1, NAT2 Polymorphisms and Pharmacokinetic Variability of Rifampicin and Isoniazid in Tuberculosis Patients from Sub-Saharan Africa
AUTHORS:
Sekossounon Sanni, Ablo Prudence Wachinou, Corinne Simone Colette Merle, Lamine Baba-Moussa, Dissou Affolabi
KEYWORDS:
Polymorphism, SLCO1B1, NAT2, Rifampicin, Isoniazid
JOURNAL NAME:
Journal of Tuberculosis Research,
Vol.10 No.3,
August
29,
2022
ABSTRACT: SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic
(PK). The objective of this study was to identify in African patients with
tuberculosis (TB) or TB/HIV co-infection,
the SLCO1B1 and NAT2
polymorphisms, associated with the variability of Rifampicin and
Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin,
Guinea, Senegal, and South Africa were included in this study. The blood
samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of
the samples were quantified using a fluorimetric method to select suitable
samples for the preparation of 96-well microplates, containing 100 μl of DNA
extract per well at the concentration of 20 ng/μl.
Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data
were analyzed and the polymorphisms with a call rate Hardy-Weinberg
Equilibrium (HWE) were excluded. The correlation
between significant genetic polymorphisms, the clearance,
and the AUC were tested by a multiple linear regression model using the PLINK2
software. Out of 385 samples, five (05) were excluded after quality controls.
After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium.
Finally, 378 samples and 318,751 SNPs were included in the genetic analyses.
The SLCO1B1 and NAT2 polymorphisms
were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected
patients from Sub-Saharan Africa.