Article

Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the LIFE study.

Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
Pharmacogenetics and Genomics (Impact Factor: 3.45). 02/2010; 20(2):77-85. DOI: 10.1097/FPC.0b013e328333f70b
Source: PubMed

ABSTRACT This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol.
We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol.
ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH.
ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.

0 Followers
 · 
121 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension pharmacogenomics holds the promise of leading to individualized drug treatment approaches for the approximately 1 billion individuals worldwide with hypertension. Prior to 2000, the literature on hypertension pharmacogenomics was quite limited. The last decade has seen a substantial growth in the literature, with several examples of genes that appear to play an important role in antihypertensive response. The last decade has also made apparent the numerous challenges in hypertension pharmacogenomics, and addressing those challenges will be important. Moving forward, it seems clear that collaboration among researchers to allow replication or joint analyses will be essential in advancing the field, as will the use of genome-wide association approaches. The next decade should clearly define the clinical potential for hypertension pharmacogenomics.
    Pharmacogenomics 04/2010; 11(4):487-91. DOI:10.2217/pgs.10.34 · 3.43 Impact Factor
  • Pharmacogenomics 10/2010; 11(10):1345-8. DOI:10.2217/pgs.10.124 · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Drug-drug interactions can lead to reduced efficacy of medical treatment. Therapeutic failure may for instance result from combined treatment with an inhibitor of the specific pathway that is responsible for the generation of pharmacologically active drug metabolites. This problem may be overlooked in clinical practice. Several examples of drugs will be discussed -clopidogrel, losartan, tamoxifen and codeine - to illustrate differences in the potential impact on drug treatment in clinical practice. We conclude that the combined use of cytochrome P450-blocking serotonin reuptake inhibitors and tamoxifen or codeine should be avoided, whereas the situation is much more complex regarding the use of proton pump inhibitors together with clopidogrel, and the evidence regarding cytochrome P450 inhibitor-dependent activation of losartan is inconclusive.
    Journal of Internal Medicine 12/2010; 268(6):540-8. DOI:10.1111/j.1365-2796.2010.02303.x · 5.79 Impact Factor