Beta1- and alpha2c-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry.
BACKGROUND
Although the beta1-adrenoreceptor (AR) Gly389Arg and alpha2c-AR Del322-325 gene variants are associated with the response to beta-AR-blocker therapy, whether this effect is associated with the risk for heart failure, or the severity or progression of heart failure is uncertain.


OBJECTIVE
To assess the relationship between Gly389Arg and Del322-325 variants and the presence, severity and progression of idiopathic dilated cardiomyopathy (IDC) in 403 black South African patients.


METHODS
Genotypes were identified using a restriction fragment length polymorphism-based technique and automated sequencing. Left ventricular ejection fraction (LVEF) and dimensions were determined at baseline and in 132 patients after six months of standard medical therapy excluding beta-AR-blockers (not indicated as standard care at the time of completing this study).


RESULTS
All patients and controls genotyped for the alpha2c-AR variant were homozygous for the Del322-325 (risk) allele. The Gly389Arg polymorphism was not associated with IDC (control n = 429) (Arg389 allele homozygosity: odds ratio = 1.03, confidence limits = 0.78-1.35), nor did it predict LVEF and cavity dimensions either before or after therapy.


CONCLUSIONS
In patients homozygous for the risk allele of the alpha2c-AR variant, the beta1-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving beta-AR-blockers.
Woodiwiss
A J
AJ
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Division of Cardiology, Chris-Hani Baragwanath Hospital and University of the Witwatersrand, Johannesburg. angela.woodiwiss@wits.ac.za
Badenhorst
D
D
Sliwa
K
K
Brooksbank
R
R
Essop
R
R
Sareli
P
P
Norton
G R
GR
D044383:Black People / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D013019:South Africa; D013318:Stroke Volume / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics
C547774:ADRA2C protein, human; D002317:Cardiovascular Agents; D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1
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