Abstract：
BACKGROUND: Pharmacogenetic research has led to significant progress in understanding how genetic factors influence drug response in tuberculosis (TB) treatment. One ongoing challenge is the variable occurrence of adverse drug reactions in some TB patients. Previous studies have indicated that genetic variations in the N-acetyltransferase 2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) genes can impact the blood concentrations of the first-line anti-TB drugs isoniazid (INH) and rifampicin (RIF), respectively. This study aimed to investigate the influence of pharmacogenetic markers in the NAT2 and SLCO1B1 genes on TB treatment outcomes using whole-exome sequencing (WES) analysis.
METHODS: DNA samples were collected from 30 healthy Iranian adults aged 18-40 years. The allelic frequencies of single-nucleotide polymorphisms (SNPs) in the NAT2 and SLCO1B1 genes were determined through WES.
RESULTS: Seven frequent SNPs were identified in the NAT2 gene (rs1041983, rs1801280, rs1799929, rs1799930, rs1208, rs1799931, rs2552), along with 16 frequent SNPs in the SLCO1B1 gene (rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs2291075, rs201722521, rs11045852, rs11045854, rs756393362, rs11045859, rs74064211, rs201556175, rs34671512, rs71581985, rs4149085).
CONCLUSIONS: Genetic variations in NAT2 and SLCO1B1 can affect the metabolism of INH and RIF, respectively. A better understanding of the pharmacogenetic profile in the study population may facilitate the design of more personalized and effective TB treatment strategies. Further research is needed to directly correlate these genetic markers with clinical outcomes in TB patients.
METHODS: DNA samples were collected from 30 healthy Iranian adults aged 18-40 years. The allelic frequencies of single-nucleotide polymorphisms (SNPs) in the NAT2 and SLCO1B1 genes were determined through WES.
RESULTS: Seven frequent SNPs were identified in the NAT2 gene (rs1041983, rs1801280, rs1799929, rs1799930, rs1208, rs1799931, rs2552), along with 16 frequent SNPs in the SLCO1B1 gene (rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs2291075, rs201722521, rs11045852, rs11045854, rs756393362, rs11045859, rs74064211, rs201556175, rs34671512, rs71581985, rs4149085).
CONCLUSIONS: Genetic variations in NAT2 and SLCO1B1 can affect the metabolism of INH and RIF, respectively. A better understanding of the pharmacogenetic profile in the study population may facilitate the design of more personalized and effective TB treatment strategies. Further research is needed to directly correlate these genetic markers with clinical outcomes in TB patients.
摘要：
背景：药物遗传学研究在理解遗传因素如何影响结核病（TB）治疗中的药物反应方面取得了重大进展。一个持续的挑战是一些结核病患者中药物不良反应的可变发生率。先前的研究表明，N-乙酰转移酶2（NAT2）和溶质载体有机阴离子转运蛋白家族成员1B1（SLCO1B1）基因的遗传变异可以影响一线抗结核药物异烟肼（INH）和利福平（RIF）的血液浓度。分别。本研究旨在使用全外显子组测序（WES）分析研究NAT2和SLCO1B1基因中药物遗传学标记对结核病治疗结果的影响。
方法：从30名18-40岁的伊朗健康成年人中收集DNA样本。通过WES确定NAT2和SLCO1B1基因中单核苷酸多态性（SNP）的等位基因频率。
结果：在NAT2基因中鉴定出七个常见的SNP（rs1041983，rs1801280，rs1799929，rs1799930，rs1208，rs1799931，rs2552），以及SLCO1B1基因中的16个常见SNPs(rs2306283,rs11045818,rs11045819,rs4149056,rs4149057,rs2291075,rs201722521,rs11045852,rs45110854,rs756393362,rs11045859,r15s2014064srs
结论：NAT2和SLCO1B1的遗传变异可影响INH和RIF的代谢，分别。更好地了解研究人群中的药物遗传学特征可能有助于设计更个性化和有效的结核病治疗策略。需要进一步的研究将这些遗传标记与结核病患者的临床结果直接相关。
方法：从30名18-40岁的伊朗健康成年人中收集DNA样本。通过WES确定NAT2和SLCO1B1基因中单核苷酸多态性（SNP）的等位基因频率。
结果：在NAT2基因中鉴定出七个常见的SNP（rs1041983，rs1801280，rs1799929，rs1799930，rs1208，rs1799931，rs2552），以及SLCO1B1基因中的16个常见SNPs(rs2306283,rs11045818,rs11045819,rs4149056,rs4149057,rs2291075,rs201722521,rs11045852,rs45110854,rs756393362,rs11045859,r15s2014064srs
结论：NAT2和SLCO1B1的遗传变异可影响INH和RIF的代谢，分别。更好地了解研究人群中的药物遗传学特征可能有助于设计更个性化和有效的结核病治疗策略。需要进一步的研究将这些遗传标记与结核病患者的临床结果直接相关。
