Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

2008

Interactions Between Adrenergic Receptors Affect Heart Failure Survival

Sample size: 655 publication 10 minutes Evidence: moderate

Author Information

Author(s): Kardia Sharon LR, Kelly Reagan J, Keddache Mehdi A, Aronow Bruce J, Grabowski Gregory A, Hahn Harvey S, Case Karen L, Wagoner Lynne E, Dorn Gerald W II, Liggett Stephen B

Primary Institution: Department of Epidemiology, School of Public Health, University of Michigan

Hypothesis

The study investigates the synergistic effects of polymorphisms in the ADRA2C and ADRB1 genes on the risk of death or transplant in heart failure patients.

Conclusion

Multiple polymorphisms act synergistically between the ADRA2C and ADRB1 genes to increase risk of death or cardiac transplant in heart failure patients.

Supporting Evidence

Three polymorphisms in ADRA2C and five in ADRB1 were involved in significant interactions.
The relative risk of death or transplant was 3.35 when combining high-risk genotype classes.
Only intergenic epistasis was observed, with no evidence of intragenic interactions.
Four polymorphisms significantly deviated from Hardy-Weinberg equilibrium.
The study used cross-validation methods to reduce false positives.

Takeaway

This study found that certain genetic changes in heart failure patients can work together to make them more likely to die or need a heart transplant.

Methodology

The study genotyped 16 sequence variations in ADRA2C and 17 in ADRB1 in a cohort of heart failure patients and used Cox proportional hazards modeling to analyze the data.