Relationship between beta1-adrenergic receptor polymorphisms and cardiovascular disease in patients with diabetic nephropathy.
OBJECTIVE
Activation of beta1-adrenergic receptor (beta1AR) enhances contractility and heart rate. The polymorphism Arg389Gly in the beta1AR gene was found to be functionally important in determining receptor activity. The relationship between this polymorphism and the risk of cardiovascular disease was investigated in Chinese subjects with overt diabetic nephropathy.


METHODS
A total of 219 type 2 diabetic subjects with nephropathy were recruited. Genotyping of the beta1AR Arg389Gly polymorphism was determined. Patients were followed up to 96 months for the development of cardiovascular events.


RESULTS
There were 122, 86 and 11 patients with Arg/Arg, Arg/Gly and Gly/Gly genotype, respectively. At 96 months, the event-free survival of primary composite cardiovascular end-point was 33.0% and 44.3% for Gly(+) and Gly(-) groups, respectively (log-rank test, P = 0.105), while the event-free survival for first ischaemic heart disease was 62.4% and 75.9%, respectively (log-rank test, P = 0.038). However, with multivariate analysis by the Cox proportional hazard model to adjust for confounders, only low-density lipoprotein and baseline glomerular filtration rate were independent predictors of first ischaemic heart event.


CONCLUSIONS
The beta1AR Arg389Gly polymorphism is not an independent predictor of cardiovascular events in subjects with overt diabetic nephropathy.
Poon
Peter Yam-Kau
PY
Departments of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Szeto
Cheuk-Chun
CC
Kwan
Bonnie Ching-Ha
BC
Chow
Kai-Ming
KM
Li
Philip Kam-Tao
PK
D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D002681:China; D003928:Diabetic Nephropathies / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
C547787:ADRB1 protein, human; D018342:Receptors, Adrenergic, beta-1