Current Pharmacogenomics - Volume 2, Issue 1, 2004

This review discusses the regulatory role of the human MDR1 multidrug transporter in the traffic of drugs and xenobiotics into the body as well as into certain organs and tissues (e.g. brain, germ cells, fetus). It also explores the relevance of single nucleotide polymorphisms (SNPs) within the MDR1 gene with respect to variations in MDR1 protein expression and function. In silico methods of SNP identification in the MDR1 gene Read More

Canavan disease (CD) is an autosomal recessive disorder, caused by mutations in the aspartoacylase gene resulting enzyme deficiency. Patients with CD have accumulation of NAAG and NAA in the brain resulting elevated urinary NAAG and NAA. Aspartoacylase gene mutation in the mouse led to multiple genomic abnormalities. Pathophysiological processes implicated in CD include spongy degeneration of the brain possibly Read More

Single nucleotide polymorphisms (SNPs) represent the most common form of sequence variation in human DNA. With the completion of the human genome project, SNP genotyping is being undertaken in a large number of pharmacogenomic studies to identify variants associated with responses to specific drugs. The speed at which the goals of pharmacogenomics will be met depends on the development of a large set of SNP ma Read More

Epidemiological studies have suggested an association between an increased dietary intake of carotenoids and a reduced incidence of cancer, even if results from clinical trials indicated that β-carotene supplements do not protect against cancer and might actually increase the risk of lung cancer in smokers. Although several mechanisms by which carotenoids modulate cancer process have been reported, there are still conflicting Read More

Spermatogenesis involves action and interaction of several genes present both on the autosome and sex chromosomes. Protooncogene c-kit receptor is one such autosomal gene implicated with hematopoiesis, melanogenesis and spermatogenesis. A sizable body of literature is available on the regulatory role of this gene, its ligand “stem cell factor” and its functional conservation across the species. Sequences from the e Read More

The potential of pharmacogenomics has received widespread attention. The goals include identifying patients in whom a substantial response, or the absence of a response, to an individual drug can be anticipated; targets for drug therapy based on genetic polymorphisms involved in pathogenesis; and new opportunities for drug development. Diabetic (DM) nephropathy provides a useful model for exploring these issu Read More

NQO1 (NAD(P)H:quinone oxidoreductase-1) is a cytosolic flavoprotein that catalyses the two-electron reduction of endogenous and environmental quinones. NQO1 plays a prominent role in protecting cells from the toxic effects of quinones, oxidative stress and more recently, the stabilisation of p53. Paradoxically, NQO1 is a target for anti-cancer drug development as reduction of certain quinones can generate cytotoxic species. Read More

Diversity in response to antihypertensive therapy is well-documented. Among many variables in the biological system, reasons include the genetic make-up of individuals. Although individual human genomes are 99.9% identical, the 0.1% difference predicts as many as three million polymorphisms. Some will affect protein expression or function, resulting in phenotypes affected for disease or with altered drug respon Read More