rs2230345

This is a missense variant in the GRK5 gene.

Key Literature Trait Associations

Heart Failure and Beta-Blocker Response

GRK5 Gln41Leu (rs2230345) is a gain-of-function variant in G protein-coupled receptor kinase 5 that more effectively uncouples beta-adrenergic receptor signaling. The Leu41 variant (T allele) functions as an endogenous "genetic beta-blocker," protecting against catecholamine-induced cardiomyopathy. In African American heart failure patients, carriers showed decreased mortality and improved ejection fraction. Enriched in populations of African descent (~30%) vs Europeans (~1%).

Liggett SB et al. “A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure” Nature Medicine (2008)

Allele T

OR —

p —

Candidate gene study

Beta-Blocker Response

GRK5 Gln41Leu is a gain-of-function variant in G protein-coupled receptor kinase 5, which desensitizes beta-adrenergic receptors. The Leu41 variant acts as a natural "genetic beta-blocker" — carriers have inherent beta-adrenergic receptor desensitization, which may reduce heart failure risk and modify the clinical benefit of pharmacologic beta-blockers. This variant is more common in African American populations.

DeLuca GC et al. “An extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the HLA-DRB1 locus.” Proceedings of the National Academy of Sciences of the United States of America 104(52):20896-20901 (2007)

Allele A

OR —

p —

Candidate gene study

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Loading comments…