The human G147D-protein phosphatase 1 inhibitor-1 polymorphism is not associated with altered clinical characteristics in heart failure.
OBJECTIVE
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 beta-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 beta-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 beta-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.
Chen
Guoli
G
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA.
Zhou
Xiaoyang
X
Pathak
Anand
A
Dorn
Gerald W
GW
Kranias
Evangelia G
EG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics* / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006333:Heart Failure / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D054645:Protein Phosphatase 1; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data; D055815:Young Adult
D011506:Proteins; C450539:PPP1R2C protein, human; D054645:Protein Phosphatase 1