In summary, our data support a role of ABCB11 and ABCB4 mutations and polymorphisms in drug-induced cholestasis. Genotyping of selected patients with acquired cholestasis might help to identify individuals with a genetic predisposition.

Our data support a role for the ABCB11 1331T>C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and gamma-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

Hypertension is more frequent and more severe in some Black populations. Although many studies have focused on hypertension in black people in an attempt to understand the genetic and environmental factors that regulate blood pressure, this approach has not been productive. Study of the relationship between specific phenotypes and genotypes, both within and across ethnic groups, is more likely to advance our understanding of the regulation of blood pressure than studies focused on race and blood pressure.

BACKGROUND The Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been linked to cardiovascular disease. However, the functional consequences of this polymorphism have not been fully defined. Our aim was to investigate if this polymorphism is functionally relevant in healthy humans by having an effect on endothelial‐dependent vasodilatation. METHODS Endothelial function was assessed in 68 normal volunteers (aged 18–44y) by bilateral forearm venous occlusion plethysmography with intra‐arterial infusions of increasing doses of acetylcholine for endothelial dependent vasodilatation, sodium nitroprusside and verapamil for endothelial independent vasodilatation. Blood was genotyped by polymerase chain reaction and BanII digestion. RESULTS There were 3 genotypes: homozygous for the Glu298 variant (GG), homozygous for the Asp298 variant (TT) and heterozygous (GT). The TT genotype's vasodilatory response to the endothelial‐dependent vasodilator acetylcholine was lower than the GG variant (p=0.04) and GT variant (p=0.08) (Fig). No differences were found between the GG and GT groups (p=NS). There was also no effect of eNOS genotype on the response to the endothelial‐independent vasodilators. CONCLUSION The Asp298 variant of the eNOS gene is associated with a blunted endothelial‐dependent vasodilation in healthy subjects. These findings may provide an important insight into the pathophysiology of endothelial dysfunction in cardiovascular diseases. Clinical Pharmacology & Therapeutics (2005) 79, P65–P65; doi: