Pharmacogenomics: Where does Britain Stand?

Hudson, John

doi:10.2217/pgs.11.159

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…Going forward, newer techniques including exome arrays that can assess for functional genetic variants present in 1 in 1000 to 1 in 5,000 individuals at over 250,000 loci are being undertaken. In addition, improvements in the speed, accuracy, and costs of whole exome and whole genome sequencing now allow for a more in-depth search of causal variants from smaller samples of well phenotyped, high causality cases attributed to a single drug (137). The role of DNA methylation, copy number variants and epigenetics in most forms of acute liver injury is largely unknown but also worthy of further study (138).…”

Section: Genetic Studies In Pooled Idiosyncratic Dili Patientsmentioning

confidence: 99%

Pathogenesis of Idiosyncratic Drug-Induced Liver Injury and Clinical Perspectives

2014

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Idiosyncratic drug-induced liver injury (DILI) is a rare disease that develops independently of drug dose, or route or duration, of administration. Furthermore, idiosyncratic DILI is not a single disease entity, but rather a spectrum of rare diseases with varying clinical, histologic, and laboratory features. The pathogenesis of DILI is not fully understood. Standardization of the DILI nomenclature and methods to assess causality, along with the information provided by the LiverTox website, will harmonize and accelerate DILI research. Studies of new serum biomarkers such as glutamate dehydrogenase, high-mobility group box-1 protein, and microRNA-122 could provide information for use in diagnosis and prognosis, and provide important insights into mechanisms of DILI pathogenesis. Single nucleotide polymorphisms in the HLA region have been associated idiosyncratic hepatotoxicity attributed to flucloxacillin, ximelagatran, lapatanib, and amoxicillin- clavulanate. However, genome-wide association studies of pooled cases have not associated any genetic factors with idiosyncratic DILI. Whole-genome and whole-exome sequencing analyses are underway to study DILI cases attributed to a single medication. Serum proteomic, transcriptome, and metabolome, along with intestinal microbiome, analyses will increase our understanding of the mechanisms of this disorder. Further improvements to in vitro and in vivo test systems should advance our understanding of the causes, risk factors, and mechanisms of idiosyncratic DILI.

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Section: Genetic Studies In Pooled Idiosyncratic Dili Patientsmentioning

confidence: 99%

Pathogenesis of Idiosyncratic Drug-Induced Liver Injury and Clinical Perspectives

2014

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“…The study of pharmacogenomics has become essential for successful drug discovery and offers widespread public health benefits [29]. For anticancer drugs, it provides an opportunity to develop superior, more targeted therapies with reduced toxicities.…”

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confidence: 99%