Pharmacogenetics and healthcare outcomes in patients with chronic heart failure
European Journal of Clinical Pharmacology, 05/16/2012
Kim KM et al. – After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1, ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.Methods
- One year–hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older.
- Medication adherence was measured.
- Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes.
- The genotypes of polymorphisms in six genes were determined: α2C–AR (ADRA2C), β 1–AR (ADRB1), β 2–AR (ADRB2), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and CYP4A11.
- Haplotypes for ADRB1 and ADRB2 were estimated.
- The genotype effects on healthcare outcomes were examined using log–linear regression models.
- Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01–0.54, P=0.022].
- Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09–0.59, P=0.006).
- Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively.
- For ADRB2, the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers (P<0.05).
- Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01–0.25, P=0.0013 and IRR 0.10, 95 % CI 0.02–0.42, P=0.006, respectively).
- The other polymorphisms showed no association with healthcare outcomes.