对临床相关的CYP2C8等位基因的全球分布及其推断的功能后果的元分析
Mahamadou D Camara1,2, Yitian Zhou1, Taís Nóbrega De Sousa3,4
1Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.
Human genomics
|April 22, 2024
概括
在CYP2C8的遗传变异影响药物代谢和安全性. 这项研究在全球范围内绘制了CYP2C8等位基因频率图,识别了由于药物代谢减少而面临药物不良反应风险的人群.
科学领域:
- 药物基因组学 药物基因组学
- 药物新陈代谢 药物新陈代谢
- 遗传变异性 遗传变异性
背景情况:
- 细胞染色体P450 2C8 (CYP2C8) 代谢了5%的处方药,包括抗疟,抗癌和抗炎药物.
- 在CYP2C8的遗传变异显著影响药物的药理动力学,疗效和安全性.
研究的目的:
- 在全球多样化的人口中全面描述CYP2C8变异性遗传格局.
- 确定CYP2C8等位基因的民族地理分布及其功能后果.
主要方法:
- 来自96项研究和数据库的数据分析,包括来自44个国家和43个族群的33185名个人.
- 基因变异的分析,包括功能减少的等位基因,如CYP2C8*2,CYP2C8*3和CYP2C8*4.
主要成果:
- 在西非和中非 (16-36.9%),CYP2C8*2等位基因最为普遍,而在欧洲和亚洲 (<2%) 则较为罕见.
- 欧洲和美洲的CYP2C8*3和CYP2C8*4常见 (分别为6.9-19.8%和2.3-7.5%),但在非洲和东亚人群中很少见.
- 观察到对等基因频率的显著民族地理差异,非洲和欧洲的20-60%的个体携带与阿莫迪亚奎因和其他CYP2C8基质的代谢减少相关的等位基因.
结论:
- 该研究提供了全球CYP2C8遗传和功能变异性的高分辨率映射.
- 结果确定了在用CYP2C8基质治疗时面临不良药物事件风险的群体.
- 高分辨率的药物遗传学分析对精准医学至关重要,特别是在研究不足的具有独特遗传特征的人群中.
相关概念视频
Single Nucleotide Polymorphisms-SNPs
15.0K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.0K
Comparing Copy Number Variations and SNPs
17.7K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.7K
Nonlinear Pharmacokinetics: Role of Transporters
48
A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
Polymorphisms occurring in drug transporters can alter...
48
Analysis of Population Pharmacokinetic Data
252
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
252
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
131
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
131
Genome-wide Association Studies-GWAS
13.4K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.4K


