Thai pharmacogenomics database −2 (TPGxD-2) sequel to TPGxD-1, analyzing genetic variants in 26 non-VIPGx genes within the Thai population

IF 3.1 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Cts-Clinical and Translational Science Pub Date : 2024-10-25 DOI:10.1111/cts.70019

Shobana John, Sommon Klumsathian, Paravee Own-eium, Angkana Charoenyingwattana, Jakris Eu-ahsunthornwattana, Thanyachai Sura, Donniphat Dejsuphong, Piyamitr Sritara, Prin Vathesatogkit, Nartthawee Thongchompoo, Wiphaporn Thabthimthong, Nuttinee Teerakulkittipong, Wasun Chantratita, Chonlaphat Sukasem

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Abstract

Next-generation sequencing (NGS) has transformed pharmacogenomics (PGx), enabling thorough profiling of pharmacogenes using computational methods and advancing personalized medicine. The Thai Pharmacogenomic Database-2 (TPGxD-2) analyzed 948 whole genome sequences, primarily from the Electricity Generating Authority of Thailand (EGAT) cohort. This study is an extension of the previous Thai Pharmacogenomic Database (TPGxD-1) and specifically focused on 26 non-very important pharmacogenes (VIPGx) genes. Variant calling was conducted using Sentieon (version 201808.08) following GATK's best workflow practices. We then annotated variant call format (VCF) files using Golden Helix VarSeq 2.5.0. Star allele analysis was performed with Stargazer v2.0.2, which called star alleles for 22 of 26 non-VIPGx genes. The variant analysis revealed a total of 14,529 variants in 26 non-VIPGx genes, with TBXAS1 had the highest number of variants (27%). Among the 14,529 variants, 2328 were novel (without rsID), with 87 identified as clinically relevant. We also found 56 known PGx variants among the known variants (n = 12,201), with UGT2B7 (19.64%), CYP1B1 (8.9%), SLCO2B1 (8.9%), and POR (8.9%) being the most common. We reported a high frequency of intermediate metabolizers (IMs) in CYP2F1 (34.6%) and CYP4A11 (8.6%), and a high frequency of decreased functional alleles in POR (53.9%) and SLCO1B3 (34.9%) genes. This study enhances our understanding of pharmacogenomic profiling of 26 non-VIPGx genes of notable clinical importance in the Thai population. However, further validation with additional computational and reference genotyping methods is necessary, and novel alleles identified in this study should undergo further orthogonal validation.

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泰国药物基因组学数据库-2（TPGxD-2）是 TPGxD-1 的续集，分析泰国人口中 26 个非 VIPGx 基因的遗传变异。

下一代测序（NGS）改变了药物基因组学（PGx），利用计算方法实现了对药物基因的全面分析，推动了个性化医疗的发展。泰国药物基因组数据库-2（TPGxD-2）分析了 948 个全基因组序列，主要来自泰国发电局（EGAT）的队列。该研究是之前泰国药物基因组数据库（TPGxD-1）的延伸，特别关注 26 个非非常重要的药物基因（VIPGx）。我们按照 GATK 的最佳工作流程实践，使用 Sentieon（201808.08 版）进行了变异调用。然后，我们使用 Golden Helix VarSeq 2.5.0 对变异调用格式 (VCF) 文件进行了注释。我们使用 Stargazer v2.0.2 对 26 个非 VIPGx 基因中的 22 个基因进行了明星等位基因分析。变异分析显示，26 个非 VIPGx 基因中共有 14,529 个变异，其中 TBXAS1 的变异数最多（27%）。在这 14529 个变异中，有 2328 个是新变异（无 rsID），其中 87 个被确定为临床相关变异。在已知变异（n = 12,201）中，我们还发现了 56 个已知的 PGx 变异，其中 UGT2B7（19.64%）、CYP1B1（8.9%）、SLCO2B1（8.9%）和 POR（8.9%）最为常见。我们发现，CYP2F1（34.6%）和 CYP4A11（8.6%）基因的中间代谢者（IMs）频率较高，而 POR（53.9%）和 SLCO1B3（34.9%）基因的功能减弱等位基因频率较高。这项研究加深了我们对泰国人群中 26 个具有显著临床重要性的非 VIPGx 基因的药物基因组分析的了解。然而，有必要使用更多的计算和参考基因分型方法进行进一步验证，本研究中发现的新等位基因也应进行进一步的正交验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cts-Clinical and Translational Science 医学-医学：研究与实验

CiteScore

6.70

自引率

2.60%

发文量

234

审稿时长

6-12 weeks

期刊介绍： Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.