L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome.

Altered response to acute catecholamine increase in the synaptic cleft is considered to be the mechanism underlying transient left ventricular apical ballooning syndrome (LVABS).We postulated that polymorphisms associated with different bAR responsiveness might play a role in the risk of LVABS. We prospectively enrolled 22 consecutive LVABS patients (4 men, age63+13 years) admitted to the Intensive Coronary Care unit of the AOP Federico II, Naples, Italy between 2005 and 2008. Peripheral blood samples were collected from each patient for genetic analysis. The results were compared with those of 740 outpatients (control) aged 50+0.4 years, 57.8% male. The following polymorphisms were analysed: rs35230616 and rs1801253 for β1AR; rs1042713, rs1042714, and rs1800888 for β 2AR; rs11554276 for Gs-protein alpha subunit (GNAS);rs17098707 and rs34679178 for GRK5.The prevalence of polymorphisms of β1AR, β2AR, and GNAS were similar between patients and controls. Conversely, the percentage of LVABS patients who presented with the rs17098707 polymorphism of the GRK5 gene was significantly higher. This is the first study demonstrating a link between a polymorphism of one of the protein kinases most expressed in the heart and stress-induced acute ventricular dysfunction. The possibility of recurrence and case reports evaluating LVABS in relatives, support a genetic approach to the pathophysiology of this syndrome.