OBJECTIVES:The b-adrenergic receptor (bAR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the b 1 AR (ADRB1), b 2 AR (ADRB2), b 3 AR (ADRB3), Gs protein alpha (GNAS1), to which all three b-receptors couple and the G protein b3 subunit (GNB3), to which b 3 ARs couple. DESIGN: A case-control genetic association study. SUBJECTS: A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation (WISE) study. MEASUREMENTS: Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made. RESULTS: Polymorphisms in the three bAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity. CONCLUSIONS: Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the bARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women.

Summary Ten patients with small cell lung cancer were treated with high dose human lymphoblastoid interferon (50-100 megaunitsm-2) for 5 days, followed by low dose interferon (3 megaunits m-2) for 3 weeks. At the end of treatment, and one month later, there was no evidence of either complete or partial response. The treatment produced fever, anorexia and weight loss, with transient leucopenia and thrombocytopenia; there was evidence of a non-cholestatic elevation of serum alanine aminotransferase, with clinical deterioration in the condition of three patients presenting with hyponatraemia. A transient hypocalcaemia during high dose therapy was also noted. It seems that lymphoblastoid interferon as a single agent is unlikely to have a role in the treatment of small cell lung cancer, and that its administration as employed in this study is associated with considerable toxicity.

Pharmacogenomics is a rapidly expanding field aimed at understanding interpatient variability in drug response through the exploration and investigation of the human genome. It is an incontrovertible fact that large interpatient variability exists in response to medications. Variation in response has existed as long as medications have been used for the prevention and treatment of disease. In many ways, the field of pharmacogenomics began serendipitously in the 1950s after seminal observations describing variability in response to medications. Examples included peripheral neuropathy from isoniazid among slow acetylator, prolonged apnea from succinylcholine caused by pseudocholinesterase deficiency, and severe hypotension from debrisoquine among cytochrome P450 (CYP) 2D6 poor metabolizers. For the next 40 years, pharmacogenetic studies focused almost exclusively on the etiologies of altered variability in pharmacokinetic responses to medications. As we entered the 1990s, pharmacogenomic studies began to include studies that examined pharmacodynamic variability in drug response. Now instead of examining only differences in drug metabolizing enzymes, scientists began to focus on genes that encode drug transporters, drug targets, and ion channels. The ultimate goal of pharmacogenomics is to be able to accurately predict, based on an individual's genomic information, which medications will provide the greatest benefit with the least harm, thus transforming medicine into an era of personalized therapeutics. This chapter provides a review of pharmacogenomics and how single nucleotide polymorphisms may impact pharmacotherapy and drug discovery. The chapter further explores the abundant recent literature as well as provides insight into some of the issues, limitations, and ethical considerations of pharmacogenomics.

Pharmacogenetics is literally a combination of pharmacology and genetics. Pharmacogenetics is the study of how an individual's genetic makeup may influence response to medications. This chapter describes examples of pharmacogenetic interactions, and the role pharmacogenetics plays and might play in clinical practice.