The Human G147D-Protein Phosphatase 1 Inhibitor-1 Polymorphism Is Not Associated with Altered Clinical Characteristics in Heart Failure

Abstract

Objectives: A human protein phosphatase inhibitor-1 polymorphism, G147D (c.440G>A, p.147G>D), has been previously demonstrated to blunt the contractile responses of cardiomyocytes to β-adrenergic agonists. The present study sought to examine whether the G147D inhibitor-1 polymorphism may be associated with specific clinical characteristics of heart failure carriers. Methods: Clinical information of 963 heart failure patients was analyzed according to race, inhibitor-1 genotype, treatment with β-blockers and mortality patterns. Results: The G147D inhibitor-1 genetic variant was found almost exclusively in black subjects and its frequency was similar between normals and heart failure patients, indicating that it was not a primary risk factor for developing heart failure. Comparison of the major cardiac functional parameters and transplant-free survival patterns between carrier and noncarrier patients did not reveal any significant differences. Furthermore, echocardiographic evaluation showed similar outcomes of β-blocker treatment between G147D carriers and noncarriers. Conclusions: The present findings indicate that the human inhibitor-1 G147D polymorphism, found almost exclusively in blacks, may act as a modifier rather than risk factor in heart failure development.