SLCO1B1 and SLC10A1 polymorphism and plasma rifampin concentrations in patients with co-morbidity tuberculosis-diabetes mellitus in Baja California, Mexico

Tuberculosis (Edinb). 2022 Sep:136:102248. doi: 10.1016/j.tube.2022.102248. Epub 2022 Aug 25.

Abstract

Rifampicin is one of the most important drugs for the treatment of tuberculosis (TB). Polymorphisms in SLCO1B1 and SLC10A1 genes are associated with impaired transporter function of drug compounds such as rifampicin. The relationship between genetic variation, clinical comorbidities, and rifampicin exposures in TB patients has not been completely elucidated. The aim of this study was to investigate the prevalence of SLCO1A1 and SLCO1B1 polymorphisms in TB and TB-DM patients and to determine their relationship with rifampicin pharmacokinetics on patients from México. Blood samples were collected in two hospitals in Baja California, Mexico from February through December 2017. Sampling included 19 patients with TB, 11 with T2DM and 17 healthy individuals. Polymorphisms genotype rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs72559746,rs2291075 and rs4603354 of SLCO1B1 and rs4646285 and rs138880008 of SLC10A1 were analyzed by Sanger's sequencing. None of the SLCO1B1 and SLC10A1 variants were significantly associated with rifampicin Cmax. TB and T2DM patients with suboptimal Cmax rifampicin levels showed wild alleles in rs11045819 and rs2291075 in SLCO1B1 SLC10A1 and SLC10A1. This is the first study to analyze SLC10A1 and SLCO1B1 polymorphisms in TB and TB-T2DM patients and healthy individuals in Mexico. Further research to confirm and extend these findings is necessary.

Keywords: Diabetes; Pharmacogenetics; Pharmacogenomics; Pharmacokinetics; Rifampin; SLCO1B1; SNP; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Genotype
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Mexico / epidemiology
  • Morbidity
  • Mycobacterium tuberculosis*
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Polymorphism, Single Nucleotide
  • Rifampin
  • Symporters / genetics*
  • Tuberculosis* / diagnosis
  • Tuberculosis* / drug therapy
  • Tuberculosis* / epidemiology

Substances

  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters, Sodium-Dependent
  • SLCO1B1 protein, human
  • Symporters
  • sodium-bile acid cotransporter
  • Rifampin