SLCO1B1, NAT2 Polymorphisms and Pharmacokinetic Variability of Rifampicin and Isoniazid in Tuberculosis Patients from Sub-Saharan Africa  

作　　者：Sekossounon Sanni Ablo Prudence Wachinou Corinne Simone Colette Merle Lamine Baba-Moussa Dissou Affolabi Sekossounon Sanni;Ablo Prudence Wachinou;Corinne Simone Colette Merle;Lamine Baba-Moussa;Dissou Affolabi(National Teaching Hospital for Tuberculosis and Pulmonary Diseases, Cotonou, Benin;Faculty of Sciences and Technology, University of Abomey-Calavi, Abomey-Calavi, Benin;Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin;Special Program for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland)

机构地区：[1]National Teaching Hospital for Tuberculosis and Pulmonary Diseases, Cotonou, Benin [2]Faculty of Sciences and Technology, University of Abomey-Calavi, Abomey-Calavi, Benin [3]Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin [4]Special Program for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland

出　　处：《Journal of Tuberculosis Research》2022年第3期111-123,共13页结核病研究（英文）

摘　　要：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&#730C until DNA extractions. The DNA extracts were then frozen at -80&#730C 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 < 95% or presenting a departure from the 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.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&#730C until DNA extractions. The DNA extracts were then frozen at -80&#730C 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 < 95% or presenting a departure from the 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.

关 键 词：POLYMORPHISM SLCO1B1 NAT2 RIFAMPICIN ISONIAZID 

分 类 号：R96[医药卫生—药理学]