Piriyapongsa Jittima, Chumnumwat Supatat, Kaewprommal Pavita, Triparn Kwankom, Suvichapanich Supharat, Udomsinprasert Wanvisa, Jittikoon Jiraphun, Shaw Philip J, Nakhonsri Vorthunju, Ngamphiw Chumpol, Wangkumhang Pongsakorn, Pithukpakorn Manop, Roothumnong Ekkapong, Wiboonthanasarn Supakit, Kuptanon Chulaluck, Jinawath Natini, Porntaveetus Thantrira, Suriyaphol Prapat, Viprakasit Vip, Pisitkun Prapaporn, Kantaputra Piranit, Tim-Aroon Thipwimol, Wattanasirichaigoon Duangrurdee, Sura Thanyachai, Suphapeetiporn Kanya, Sripichai Orapan, Khongphatthanayothin Apichai, Fucharoen Suthat, Ngamphaiboon Nuttapong, Shotelersuk Vorasuk, Mahasirimongkol Surakameth, Tongsima Sissades
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Sci Rep. 2024 Dec 28;14(1):30683. doi: 10.1038/s41598-024-79018-6.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance. On average, each Thai individual carried 14 SNPs, one to two HLA alleles, and six diplotypes with actionable phenotypic associations. Clinically important diplotypes were present in over 20% of individuals for seven genes (CYP2A6, CYP2B6, CYP2C19, CYP3A5, NAT2, SLCO1B1, and VKORC1). In addition, clinically significant SNPs with allele frequencies exceeding 20% were identified among 15 genes, including VKORC1, CYP4F2, and ABCG2. We also identified 21,211 potentially deleterious variants among 3239 genes. Of these variants, 3746 were novel. The comprehensive dataset from this study serves as a valuable resource of pharmacogenomic variants in the Thai population, which will facilitate the development of personalized drug therapies and enhance patient care in Thailand.
个体间药物反应的变异性受遗传因素的显著影响，这突出了针对特定人群的药物基因组学研究对优化临床结果的重要性。在本研究中，我们分析了949名无亲缘关系的泰国个体的全基因组测序数据，并对涉及药物药代动力学、药效学或免疫介导的药物不良反应的3239个基因进行了深入分析。我们鉴定出43个单核苷酸多态性（SNP）、134种双倍型和15个人类白细胞抗原（HLA）等位基因，所有这些都具有中度到高度的临床意义。平均而言，每个泰国个体携带14个SNP、一到两个HLA等位基因以及六种具有可采取行动的表型关联的双倍型。七种基因（CYP2A6、CYP2B6、CYP2C19、CYP3A5、NAT2、SLCO1B1和VKORC1）中，超过20%的个体存在具有临床重要性的双倍型。此外，在15个基因中鉴定出等位基因频率超过20%的具有临床意义的SNP，包括VKORC1、CYP4F2和ABCG2。我们还在3239个基因中鉴定出21,211个潜在有害变异。其中，3746个是新发现的。本研究的综合数据集是泰国人群药物基因组变异的宝贵资源，将有助于泰国个性化药物治疗的发展并提高患者护理水平。
