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中国宁夏回族人群 VIP 药代基因组学变异的遗传多态性。

Genetic polymorphisms of pharmacogenomic VIP variants in the Hui population from Ningxia Province of China.

机构信息

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, 710069, Shaanxi, China.

College of Life Science, Northwest University, Xi'an, 710127, Shaanxi, China.

出版信息

Funct Integr Genomics. 2023 Mar 17;23(2):85. doi: 10.1007/s10142-023-01021-3.

Abstract

Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among different populations. However, there is little pharmacogenomic information about the Chinese Hui population. Our research aimed to reveal the outstandingly different loci in the Hui population, and provide a theoretical foundation for personalized drug use in the Hui population, so as to facilitate more effective treatment of diseases. This study genotyped 53 VIP variants of 26 genes in 200 independent Hui individuals based on the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB). Remarkable differences in the genotype and allele frequencies between the Hui and 26 other populations from the 1000 Genomes Project were assessed using the χ test. The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in PTGS2 (rs20417), NAT2 (rs1801280), NAT2 (rs1208), ACE (rs4291), and CYP2D6 (rs1065852) were considerably different in the Hui population compared with those in the other 26 populations. Besides, using the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of ibuprofen, rofecoxib (PTGS2), captopril (ACE), citalopram, and escitalopram (CYP2D6). We also discovered other variants associated with adverse reactions to cisplatin and cyclophosphamide (NAT2). Our study indicated that the loci of PTGS2 (rs20417), NAT2 (rs1801280 and rs1208), ACE (rs4291), and CYP2D6 (rs1065852) in the Hui population were obviously different from those in the other 26 populations, which provides reliable information for predicting drug efficacy. Besides, it supplements the pharmacogenomic knowledge of the Hui population and lays the foundation for the individualized treatment for the Hui population.

摘要

药物基因组学已广泛应用于研究不同人群中的重要药物遗传学(VIP)变体。然而,关于回族人群的药物基因组学信息却很少。我们的研究旨在揭示回族人群中非常不同的基因座,并为回族人群的个体化用药提供理论基础,从而更有效地治疗疾病。本研究基于药物基因组学和药物基因组学知识库(PharmGKB),对 200 名独立的回族个体的 26 个基因中的 53 个 VIP 变体进行了基因分型。使用卡方检验评估了 1000 基因组计划中 26 个其他人群与回族人群之间基因型和等位基因频率的显著差异。PTGS2(rs20417)、NAT2(rs1801280)、NAT2(rs1208)、ACE(rs4291)和 CYP2D6(rs1065852)中的单核苷酸多态性(SNP)的基因型和等位基因频率在回族人群中与其他 26 个人群有很大差异。此外,使用 PharmGKB 数据库,我们确定了几个 VIP 变体,这些变体可能改变布洛芬、罗非昔布(PTGS2)、卡托普利(ACE)、西酞普兰和艾司西酞普兰(CYP2D6)的药物代谢。我们还发现了与顺铂和环磷酰胺(NAT2)不良反应相关的其他变体。我们的研究表明,回族人群中 PTGS2(rs20417)、NAT2(rs1801280 和 rs1208)、ACE(rs4291)和 CYP2D6(rs1065852)的基因座明显不同于其他 26 个人群,这为预测药物疗效提供了可靠信息。此外,它补充了回族人群的药物基因组学知识,为回族人群的个体化治疗奠定了基础。

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