CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases

Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits. The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasians prescribed losartan. Differences between baseline and six-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired T-test or Mann Whitney U test. Primary renal disease patients had a trend toward less favorable antiproteinuric response (−31.7±156 vs −125±323%; p=0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure (9.8±16.0 mm Hg vs −3.2±10.6 mm Hg; p=0.043) and systolic blood pressure (16.2±27.1 mm Hg vs −5.5±17.5 mm Hg; p=0.044) with CYP2C9 variants. Preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan

Cost-effectiveness analysis of genetic screening for the Taq1B polymorphism in the secondary prevention of coronary heart disease

Coronary heart disease is a major health priority area in Australia. Cholesterol-lowering agents are generally considered to be cost effective for the secondary prevention of coronary heart disease. There is growing evidence, however, that the effectiveness of statins varies from one individual to another. The Taq1B polymorphism is an example of a genetic polymorphism that is thought to influence the effectiveness of statins. The aim of the current analysis is to estimate the cost–effectiveness of genetically screening coronary heart disease and stroke patients for the Taq1B polymorphism, and prescribing statin treatment to those with the B1B2 or B2B2 forms of the gene. A health sector perspective was adopted with a maximum acceptable cost–effectiveness ratio set at AUS$50,000/disability-adjusted life year. There is an 89% probability that screening and prescribing statins to those with the B1B2 and B2B2 alleles is more cost effective than prescribing statins to all patients. Modeling the cost–effectiveness of pharmacogenetics in major areas of medicine provides useful information to help in resource allocation and decision making. Economic evaluations similar to this one will be required in the future as the results of further clinical trials to establish the effectiveness of statins based on genotype become available