Börjesson M, Magnusson Y, Hjalmarson A, Andersson B
Wallenberg Laboratory for Cardiovascular Research, Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
Eur Heart J. 2000 Nov;21(22):1853-8. doi: 10.1053/euhj.1999.1994.
The adrenergic nervous system is of major importance in congestive heart failure. No genetic polymorphism has previously been identified in the beta(1)-adrenergic receptor gene. The aim of this study was to find possible mutations in this gene and to relate such findings to morbidity and prognosis in heart failure.
Genomic DNA was extracted from blood leukocytes from patients with congestive heart failure (n=184) and from age-matched controls (n=77). The part of the beta(1)-adrenergic receptor gene corresponding to nucleotide 1-255 was amplified by polymerase chain reaction and analysed by automated sequencing. The patients were investigated by echocardiography and followed regarding symptoms and survival for 5 years. A missense mutation was identified at nucleotide position 145 in the beta(1)-adrenergic receptor gene, which predicted an amino acid substitution at position 49 (Ser49Gly). The allele frequency of the Gly49 variant was 0.13 in controls and 0.18 in patients (P=0.19). At the time of the 5-years follow-up, 62% of the patients with the wild type gene and 39% of the patients with the Ser49Gly variant had died or had experienced hospitalization (P=0.005). Patients without the mutation had significantly poorer survival compared to those with the mutation, risk ratio 2.34 (95% CI 1.30-4.20), P=0.003. In a mulivariate analysis, the risk ratio was 2.03 (95% CI 0.99-4.16) P=0.05.
A novel missense mution in the beta(1)-adrenergic receptor gene was associated with a decreased mortality risk in patients with congestive heart failure. These data suggest that the beta(1)-receptor Ser49Gly variant might be associated with altered receptor function, resulting in myocardial protection in patients with heart failure.
肾上腺素能神经系统在充血性心力衰竭中至关重要。此前尚未在β₁ - 肾上腺素能受体基因中鉴定出基因多态性。本研究的目的是寻找该基因中可能的突变，并将这些发现与心力衰竭的发病率和预后相关联。
从充血性心力衰竭患者（n = 184）和年龄匹配的对照组（n = 77）的血液白细胞中提取基因组DNA。通过聚合酶链反应扩增β₁ - 肾上腺素能受体基因中对应于核苷酸1 - 255的部分，并通过自动测序进行分析。对患者进行超声心动图检查，并随访其症状和生存情况5年。在β₁ - 肾上腺素能受体基因的核苷酸位置145处鉴定出一个错义突变，该突变预测在第49位氨基酸发生取代（Ser49Gly）。Gly49变体的等位基因频率在对照组中为0.13，在患者中为0.18（P = 0.19）。在5年随访时，野生型基因患者中有62%死亡或住院，而Ser49Gly变体患者中有39%死亡或住院（P = 0.005）。与有突变的患者相比，无突变的患者生存情况明显较差，风险比为2.34（95%可信区间为1.30 - 4.20），P = 0.003。在多变量分析中，风险比为2.03（95%可信区间为0.99 - 4.16），P = 0.05。
β₁ - 肾上腺素能受体基因中的一种新型错义突变与充血性心力衰竭患者死亡风险降低相关。这些数据表明，β₁ - 受体Ser49Gly变体可能与受体功能改变有关，从而在心力衰竭患者中起到心肌保护作用。
