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JournalISSN: 1462-2416

Pharmacogenomics 

Future Medicine
About: Pharmacogenomics is an academic journal published by Future Medicine. The journal publishes majorly in the area(s): Pharmacogenomics & Pharmacogenetics. It has an ISSN identifier of 1462-2416. Over the lifetime, 3040 publications have been published receiving 78600 citations.


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Journal ArticleDOI
TL;DR: Three ATP-binding cassette (ABC)-superfamily multidrug efflux pumps are known to be responsible for chemoresistance and the effect of various genotypes and haplotypes on the expression and function of these proteins is not yet clear, and their true impact remains controversial.
Abstract: Three ATP-binding cassette (ABC)-superfamily multidrug efflux pumps are known to be responsible for chemoresistance; P-glycoprotein (ABCB1), MRP1 (ABCC1) and ABCG2 (BCRP). These transporters play an important role in normal physiology by protecting tissues from toxic xenobiotics and endogenous metabolites. Hydrophobic amphipathic compounds, including many clinically used drugs, interact with the substrate-binding pocket of these proteins via flexible hydrophobic and H-bonding interactions. These efflux pumps are expressed in many human tumors, where they likely contribute to resistance to chemotherapy treatment. However, the use of efflux-pump modulators in clinical cancer treatment has proved disappointing. Single nucleotide polymorphisms in ABC drug-efflux pumps may play a role in responses to drug therapy and disease susceptibility. The effect of various genotypes and haplotypes on the expression and function of these proteins is not yet clear, and their true impact remains controversial.

890 citations

Journal ArticleDOI
TL;DR: Over 40 cytochrome P450 (CYP) 2D6 allelic variants have been discovered thus far, and information concerning Amerindians from North (Canada), Central and South America indicate comparatively low frequencies of CYP2D6*10, perhaps a ”founders“effect.
Abstract: Over 40 cytochrome P450 (CYP) 2D6 allelic variants have been discovered thus far. The alleles may be classified on the basis of the level of activity for which they encode CYP2D6 enzymes, into functional, non-functional and reduced function groups. CYP2D6 allele frequency is known to vary amongst racial/ethnic groups. Generally, for European Caucasians and their descendants, the functional group of alleles are predominant, with a frequency of 71%. Non-functional alleles represent 26% of the variability, mainly CYP2D6*4. In Asians and their close descendants, functional alleles represent only ~ 50% of the frequency of CYP2D6 alleles. Asians and Pacific Islanders have a high frequency (median = 41%) of a reduced function allele, CYP2D6*10, contributing to the population shift to the right of metabolic rates indicating slower metabolism. Information concerning Amerindians from North (Canada), Central and South America indicate comparatively low frequencies of CYP2D6*10, perhaps a "founders" effect. The frequency of functional alleles in Africans and African Americans is also about 50%. Both Africans and African Americans have reduced function alleles representing 35% of allele variation, mainly CYP2D6*17. African Americans, however, have more than twice the median frequency of nonfunctional alleles compared with Africans (14.5% vs 6.3%). Non-functional and reduced function alleles represent about 50% of allele frequency in Black populations but a much greater variety than carried in Asians. Since alleles which encode for no or reduced functioning clearly affect metabolic activity of drugs mediated by CYP2D6, studies are needed in populations in which these alleles play a major role in order to assure optimal dosing recommendations are based on empirical pharmacogenetics.

686 citations

Journal ArticleDOI
TL;DR: High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid, and a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.
Abstract: High-resolution melting of DNA is a simple solution for genotyping, mutation scanning and sequence matching. The melting profile of a PCR product depends on its GC content, length, sequence and heterozygosity and is best monitored with saturating dyes that fluoresce in the presence of double-stranded DNA. Genotyping of most variants is possible by the melting temperature of the PCR products, while all variants can be genotyped with unlabeled probes. Mutation scanning and sequence matching depend on sequence differences that result in heteroduplexes that change the shape of the melting curve. High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid. Owing to its simplicity and speed, the method is a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.

653 citations

Journal ArticleDOI
TL;DR: This review discusses the key methodological issues in the set-up, information gathering and processing, and analysis of meta-analyses of genome-wide association datasets, and illustrates the application ofMeta-analysis methods in the elucidation of common genetic variants associated with Type 2 diabetes.
Abstract: The advent of genome-wide association studies has allowed considerable progress in the identification and robust replication of common gene variants that confer susceptibility to common diseases and other phenotypes of interest. These genetic effect sizes are almost invariably moderate to small in magnitude and single studies, even if large, are underpowered to detect them with confidence. Meta-analysis of many genome-wide association studies improves the power to detect more associations, and to investigate the consistency or heterogeneity of these associations across diverse datasets and study populations. In this review, we discuss the key methodological issues in the set-up, information gathering and processing, and analysis of meta-analyses of genome-wide association datasets. We illustrate, as an example, the application of meta-analysis methods in the elucidation of common genetic variants associated with Type 2 diabetes. Finally, we discuss the prospects and caveats for future application of meta-...

501 citations

Journal ArticleDOI
TL;DR: Age-associated changes were more pronounced than those related to differences in sex or race in the population group the authors studied, and those that were found to be statistically altered with age, sex orRace were found.
Abstract: Objective: It is well established that disease states are associated with biochemical changes (e.g., diabetes/glucose, cardiovascular disease/cholesterol), as are responses to chemical agents (e.g., medications, toxins, xenobiotics). Recently, nontargeted methods have been used to identify the small molecules (metabolites) in a biological sample to uncover many of the biochemical changes associated with a disease state or chemical response. Given that these experimental results may be influenced by the composition of the cohort, in the present study we assessed the effects of age, sex and race on the relative concentrations of small molecules (metabolites) in the blood of healthy adults. Methods: Using gas- and liquid-chromatography in combination with mass spectrometry, a nontargeted metabolomic analysis was performed on plasma collected from an age- and sex-balanced cohort of 269 individuals. Results: Of the more than 300 unique compounds that were detected, significant changes in the relative concentra...

447 citations

Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
202350
202298
2021112
2020128
2019121
2018132