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墨西哥下加利福尼亚州合并结核病-糖尿病患者中 SLCO1B1 和 SLC10A1 多态性与利福平血药浓度的关系。

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

机构信息

Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, Mexico; Posgrado Ecología Molecular y Biotecnología, Facultad de Ciencias Marinas, Universidad Autónoma de Baja California, Ensenada, Baja California, Mexico.

Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, Mexico.

出版信息

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 C. TB and T2DM patients with suboptimal C 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.

摘要

利福平是治疗结核病(TB)最重要的药物之一。SLCO1B1 和 SLC10A1 基因的多态性与药物化合物如利福平的转运蛋白功能受损有关。遗传变异、临床合并症与 TB 患者利福平暴露之间的关系尚未完全阐明。本研究旨在调查墨西哥 TB 和 TB-DM 患者中 SLCO1A1 和 SLCO1B1 多态性的流行情况,并确定其与利福平药代动力学的关系。2017 年 2 月至 12 月,在墨西哥下加利福尼亚的两家医院采集血样。采样包括 19 例 TB 患者、11 例 T2DM 患者和 17 例健康对照者。通过 Sanger 测序分析 SLCO1B1 的 rs2306283、rs11045818、rs11045819、rs4149056、rs4149057、rs72559746、rs2291075 和 rs4603354 以及 SLC10A1 的 rs4646285 和 rs138880008 多态性。SLCO1B1 和 SLC10A1 中的任何变体均与利福平 C 无显著相关性。利福平 C 水平不理想的 TB 和 T2DM 患者在 SLCO1B1 SLC10A1 和 SLC10A1 中显示出 rs11045819 和 rs2291075 的野生等位基因。这是首次在墨西哥分析 TB 和 TB-T2DM 患者及健康对照者中 SLC10A1 和 SLCO1B1 多态性的研究。需要进一步的研究来证实和扩展这些发现。

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