Yadav Anamika, Srivastava Shivani, Tyagi Shivani, Krishna Neelam, Katara Pramod
Computational Omics Lab, Centre of Bioinformatics, University of Allahabad, Prayagraj, 211002 India.
Centre of Biotechnology, University of Allahabad, Prayagraj, 211002 India.
In Silico Pharmacol. 2023 Jul 19;11(1):17. doi: 10.1007/s40203-023-00154-4. eCollection 2023.
Drugs pharmacology is defined by pharmacokinetics and pharmacodynamics and both of them are affected by genetic variability. Genetic variability varies from population to population, and sometimes even within the population, it exists. Single nucleotide polymorphisms (SNPs) are one of the major genetic variability factors which are found to be associated with the pharmacokinetics and pharmacodynamics process of a drug and are responsible for variable drug response and clinical phenotypes. Studies of SNPs can help to perform genome-wide association studies for their association with pharmacological and clinical events, at the same time; their information can direct genome-wide association studies for their use as biomarkers. With the aim to mine and characterize Indian populated SNPs of pharmacological and clinical importance. Two hundred six candidate SNPs belonging to 43 genes were retrieved from Indian Genome Variation Database. The distribution pattern of considered SNPs was observed against all five world super-populations (AFR, AMR, EAS, EUR, and SAS). Further, their annotation was done through SNP-nexus by considering Human genome reference builds - hg38, pharmacological and clinical information was supplemented by PharmGKB and ClinVar database. At last, to find out the association between SNPs linkage disequilibrium was observed in terms of r. Overall, the study reported 53 pharmaco-clinical active SNPs and found 24 SNP-pairs as potential markers, and recommended their clinical and experimental validation.
The online version contains supplementary material available at 10.1007/s40203-023-00154-4.
药物药理学由药物代谢动力学和药效学定义，而这两者都会受到基因变异性的影响。基因变异性在不同人群之间存在差异，有时甚至在同一人群内部也存在。单核苷酸多态性（SNP）是主要的基因变异因素之一，已发现其与药物的药物代谢动力学和药效学过程相关，并导致药物反应和临床表型的差异。对SNP的研究有助于开展全基因组关联研究，以探究其与药理学和临床事件的关联；同时，其信息可指导全基因组关联研究将其用作生物标志物。旨在挖掘和表征具有药理学和临床重要性的印度人群SNP。从印度基因组变异数据库中检索了属于43个基因的206个候选SNP。针对所有五个世界超级人群（非洲人、美洲人、东亚人、欧洲人、南亚人）观察了所考虑SNP的分布模式。此外，通过SNP-nexus并参考人类基因组参考版本 - hg38进行注释，药理学和临床信息由PharmGKB和ClinVar数据库补充。最后，为了找出SNP之间的关联，观察了连锁不平衡的r值。总体而言，该研究报告了53个具有药物临床活性的SNP，并发现24对SNP为潜在标志物，并建议对其进行临床和实验验证。
在线版本包含可在10.1007/s40203-023-00154-4获取的补充材料。
