No evidence for an association between the -36A>C phospholamban gene polymorphism and a worse prognosis in heart failure.
BACKGROUND
In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF.


METHODS
We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients.


RESULTS
No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed.


CONCLUSIONS
Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans.
Santos
Diogo G B
DG
Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), Sao Paulo University Medical School, Sao Paulo, Brazil. diogobiagi@gmail.com
Medeiros
Alessandra
A
Brum
Patrícia C
PC
Mill
José G
JG
Mansur
Alfredo J
AJ
Krieger
José E
JE
Pereira
Alexandre C
AC
D000328:Adult; D000368:Aged; D001938:Brazil; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D016277:Ventricular Function, Left; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000099211:Phospholamban