title: Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure.
abstract: BACKGROUND
  G-protein receptor kinase 5 (GRK5) Gln41 > Leu and β1-adrenergic receptor (ADRB1) Arg389 > Gly polymorphisms presented the different distribution of genotype frequencies between Caucasian American and African American, and produced the difference in β-blocker treatment effect among them with systolic heart failure (SHF).
  
  
  OBJECTIVE
  This study sought to identify the distributed characteristics of these variant genotypes in Chinese population, and influence of GRK5 and ADRB1 polymorphisms on SHF morbidity and β-blocker treatment effect in patients with SHF.
  
  
  METHODS
  This study was based on cross-sectional survey data. 1794 and 1718 subjects' ADRB1 and GRK5 gene sequencing (sanger method) data were achieved respectively. Blood samples collection, clinical laboratory detection, electrocardiogram and echocardiography examinations were performed. Medication usage was confirmed at in-hospital visits or the questionnaire by personal interview.
  
  
  RESULTS
  GRK5 Leu41Leu genotype was not found in our Chinese population. In non-SHF population, allele frequencies of GRK5 Gln41 and Leu41 were 2782 (0.992) and 22 (0.008) (Hardy-Weinberg equilibrium test χ(2) = 0.088, P = 0.767), and allele frequencies of ADRB1 Arg389 and Gly389 were 2127 (0.715) and 849 (0.285) (χ(2) = 0.272, P = 0.602). In SHF patients, allele frequencies of Gln41 and Leu41 were 446 (0.991) and 4 (0.009) (χ(2) = 0.018, P = 0.893), and allele frequencies of Arg389 and Gly389 were 331 (0.726) and 125 (0.274) (χ(2) = 1.892, P = 0.169). Further in logistic regression model, these ADRB1 and GRK5 variants were not significantly independently associated with the risk of SHF morbidity. Those carrying genotype ADRB1 Gly389Gly did not reduce significantly the risk of SHF morbidity after β-blocker therapy.
  
  
  CONCLUSIONS
  GRK5 Leu41Leu genotype was not found in our Chinese population, neither ADRB1 nor GRK5 variants presented independently associated with the risk of SHF morbidity, most ADRB1 and GRK5 polymorphisms did decrease significantly the risk of SHF morbidity after β-blocker therapy except for those carrying genotype ADRB1 Gly389Gly.
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. kangsheng2008@163.com.
authors: Sheng
authors: S
authors: Kang
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. hxseh@126.com.
authors: Xuan
authors: X
authors: Hong
authors: Department of Cardiology, Shanghai the 8th People's Hospital, Caobao Road 8, 200235, Shanghai, China. ruancw@yahoo.cn.
authors: Chang-wu
authors: CW
authors: Ruan
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. wuyuwu95@yahoo.com.cn.
authors: Ping
authors: P
authors: Yu
authors: Department of Clinical Laboratory, Shanghai East Hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. shanshansh@126.com.
authors: Shan-shan
authors: SS
authors: Yu
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. mingchen1283@vip.163.com.
authors: Ming
authors: M
authors: Chen
authors: Department of Cardiology, Pudong New District People's Hospital, Chuan Ring Road 490, 201299, Shanghai, China. ZDF@medmail.com.cn.
authors: Dai-fu
authors: DF
authors: Zhang
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. frankfan@tongji.edu.cn.
authors: Hui-min
authors: HM
authors: Fan
authors: Department of cardiology, Shanghai East hospital, Tongji University, Jimo Rd 150, 200120, Shanghai, P. R. China. liu.zhongmin@tongji.edu.cn.
authors: Zhong-min
authors: ZM
authors: Liu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D001483:Base Sequence; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics*; D054143:Heart Failure, Systolic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C547787:ADRB1 protein, human; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human
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