Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure
| Autor: | Zhongmin Liu, Chang-wu Ruan, Huimin Fan, Ping Yu, Sheng Kang, Ming Chen, Xuan Hong, Dai-Fu Zhang, Shanshan Yu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
G-Protein-Coupled Receptor Kinase 5
medicine.medical_specialty Multivariate analysis Population Adrenergic beta-Antagonists Molecular Sequence Data Biology Bioinformatics Logistic regression Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology symbols.namesake Internal medicine Genotype medicine Humans education Allele frequency Sanger sequencing Medicine(all) education.field_of_study Base Sequence Models Genetic Biochemistry Genetics and Molecular Biology(all) Research General Medicine Sequence Analysis DNA medicine.disease Genotype frequency Heart failure Multivariate Analysis symbols Receptors Adrenergic beta-1 Heart Failure Systolic |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | 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 χ2 = 0.088, P = 0.767), and allele frequencies of ADRB1 Arg389 and Gly389 were 2127 (0.715) and 849 (0.285) (χ2 = 0.272, P = 0.602). In SHF patients, allele frequencies of Gln41 and Leu41 were 446 (0.991) and 4 (0.009) (χ2 = 0.018, P = 0.893), and allele frequencies of Arg389 and Gly389 were 331 (0.726) and 125 (0.274) (χ2 = 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. |
| Databáze: | OpenAIRE |
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