PREVALENCE OF POLYMORPHIC CYP2C19 ALLELES PR

多态性 CYP2C19 等位基因 PR 的患病率

• 批准号: 7720572
• 负责人: Jorge Duconge
• 金额: $ 2.12万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720572
• 关键词: Algorithms; Alleles; Benefits and Risks; Biological Markers; Blood; CYP2C19 gene; Clinical; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Dose; Drug Exposure; Enzymes; Frequencies; Funding; Genetic; Genetic Polymorphism; Genotype; Goals; Grant; Hematologic Agents; Human; Individual Differences; Institution; Knowledge; Leukocytes; Modification; Molecular Biology; Molecular Biology Techniques; Peripheral; Pharmaceutical Preparations; Pharmacogenetics; Pilot Projects; Polymerase Chain Reaction; Population; Prevalence; Puerto Rican; Research; Research Personnel; Resources; Risk Assessment; Sampling; Source; Spottings; United States National Institutes of Health; Variant; enzyme substrate; interest; progesterone 11-hemisuccinate-(2-iodohistamine); response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot study to be conducted as our first step in developing a pharmacogenetic (PGt)-guided approach of dose optimization. Identification and characterization of genetic polymorphisms (biomarkers) in drug metabolizing enzymes may provide substantial knowledge about the mechanisms of inter-individual differences in drug response and, consequently, it should be incorporated in risk assessment and treatment decision (i.e., by knowing in advance who should be treated with what and how). Human CYP450 enzymes are known to be involved in the modification and/or degradation of such drugs. The genetic differences in CYP450 enzymes gives rise to important interindividual and interethnic variability in blood drug exposure and may cause differences in clinical responses. Subjects who are poor metabolizer may be more susceptible than extensive metabolizer to those drugs that are substrate of these enzymes. Accordingly, the first step in this effort will be to determine the frequencies of potential poor and extensive metabolizers as well as carriers for each clinically and functionally relevant variants of CYP450 enzymes in Puerto Ricans. Noteworthy, this information in Puerto Ricans is still an open question that remains to be determined. In this study, we are aimed at determining the genotype profile of a random Puerto Rican population in order to define prevalence of major variant alleles among Puerto Ricans. Frequencies for the major CYP2C19 alleles will be evaluated in human DNA samples (about 500) present in blood spots on Guthrie cards. Genotyping will be carried out on peripheral leukocytes DNA by molecular biology techniques (i.e., DNA extraction and purification, amplification by PCR, analysis by PG micro-array and/or DHPLC).The long-term goal is to generate valuable data from the genetic background of Puerto Ricans in order to develop appropriate dosing algorithm for any CYP450 drug substrate of clinical interest, that maximize the benefit - risk relationship.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项试点研究，是我们开发剂量优化的药物遗传学（PGT）指导方法的第一步。药物代谢酶中遗传多态性（生物标志物）的鉴定和表征可以提供有关药物反应中个体间差异的机制的大量知识，因此，应将其纳入风险评估和治疗决策中（即，通过事先了解谁应接受什么以及如何处理以及如何处理）。已知人类CYP450酶参与此类药物的修饰和/或降解。 CYP450酶的遗传差异会导致血液药物暴露的重要间和种族间变异性，并可能导致临床反应的差异。较差的代谢者的受试者可能比广泛的代谢剂更容易受到这些酶底物的代谢。因此，这项工作的第一步将是确定波多黎各人中CYP450酶的每个临床和功能相关变体的潜在贫困和广泛代谢物的频率以及载体。值得注意的是，波多黎各人中的这些信息仍然是一个悬而未决的问题，尚待确定。在这项研究中，我们旨在确定波多黎各人口随机的基因型谱，以确定波多黎各人的主要变体等位基因的流行。主要CYP2C19等位基因的频率将在Guthrie卡上的血点中评估（约500个）。基因分型将通过分子生物学技术（即DNA提取和纯化，通过PCR进行扩增，PG微观阵列和/或DHPLC分析）对外周白细胞DNA进行DNA进行。长期目标是从适当的ALGORITH中产生适当的ALGORITH INSTRATE ALGORITH ALGORITH PORTTRATIOL PARTERITICTION ALGORTRES PORTTRATIOL PARTRETICS ALGORTRES PORTTRATIC PORTTRATE ALGORTRETIM dODOSS ALGORTRATES的依赖的caltrate Algority量的依赖的基因的目标。兴趣，最大化利益 - 风险关系。