Genetic beta-blockade?

Genetic beta-blockade?

G protein-coupled receptor (GPCR) kinases (GRKs) – e.g. GRK5, GRK6 – are important regulators of GPCR function. L41Q (glutamine at position 41 is replaced by leucine) polymorphism in the GRK5 gene has been associated with decreased mortality in African Americans with heart failure or cardiac ischemia. In a prospective study involving three hundred and seventy five persons with heart failure, GRK5-L41 polymorphism conferred protected against death or cardiac transplantation.This GRK5 polymorphism is thought to inhibit beta-adrenergic receptor signaling and thereby acts as a form of ‘genetic beta-blockade’ [Liggett SB, et al. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat Med. 2008;14:510-7]. GRK5-Leu41 has been shown to give protection against experimental catecholamine-induced cardiomyopathy.