Pharmacogenetics and pharmacogenomics of cholesterol-lowering therapy.

Purpose Of Review: To summarize recent findings on pharmacokinetics, pharmacodynamics, drug-drug interactions and influence of lifestyle heterogeneity on adverse events in cholesterol-lowering therapy

Recent Findings: The prevention of cardiovascular disease is critically dependent on lipid-lowery therapy, including statins, cholesterol absorption inhibitors, fibrates and nicotinic acid. Statins are the most prescribed drugs in lipid lowering therapy with variability in response and almost one third of the patients do not meet their treatment goals. The severe adverse effects of treatment with cerivastatin stimulated the search for new genes and gene variations affecting pharmacokinetics, drug-drug interactions and pharmacodynamics.

Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease.

Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelial barrier function in this disease. Therefore, ileal and colonic mucosal biopsies from nonaffected regions of patients with ulcerative colitis (UC) and Crohn's disease (CD), as well as non-IBD probands, were subjected to Affymetrix DNA-microarray analysis.

Cloning and characterization of a novel apolipoprotein A-I binding protein, AI-BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA-I.

Apolipoprotein A-I (apoA-I) is the major apolipoprotein of high-density lipoproteins (HDL) and has an important role in the regulation of the stability, lipid transport, and metabolism of HDL particles. To identify novel proteins that are involved in HDL metabolism, we used mature apoA-I (amino acids 25-267) as a bait for the screening of a human liver two-hybrid cDNA library. Among the identified genes, several encoded known proteins, including serum amyloid A(2a) (SAA(2a)), apoC-I, and phosphodiesterase HCAM1 (PDE1A), found to interact with apoA-I.