β-1肾上腺素能受体阻滞剂与雷诺现象风险之间的关联：孟德尔随机化研究
Association between beta-1-adrenoceptor blockade and risk of Raynaud's phenomenon: Mendelian randomisation study.
作者信息
Williams Jacob C, Rogers Kira, Coulson Kathryn, Hughes David M, Hughes Michael, Zhao Sizheng Steven
机构信息
St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
出版信息
J Scleroderma Relat Disord. 2025 Mar 25:23971983241312543. doi: 10.1177/23971983241312543.
INTRODUCTION/OBJECTIVES: Raynaud's phenomenon is a common vasospastic disorder associated with reduced health-related quality of life and, occasionally, ischaemic tissue damage depending on aetiology. The effect of beta-1-adrenoceptor blockers (e.g. bisoprolol, atenolol) on Raynaud's phenomenon remains unclear. We aimed to assess the association between genetically mimicked beta-1-adrenoceptor blockade and the risk of Raynaud's phenomenon.
METHODS
We used two protein-coding single nucleotide polymorphisms in the gene, rs1801252 (A > G; Ser49Gly) and rs1801253 (G > C; Arg389Gly), to derive an unweighted allele count as the instrumental variable, using individual-level UK Biobank data. Raynaud's phenomenon was defined using International Classification of Diseases or Read codes. We used the ratio method and analysis was performed separately using systolic and diastolic blood pressure as the biomarker. To examine the validity of this approach and the Raynaud's phenomenon case definition, we also tested the known association between phosphodiesterase-5 inhibition and Raynaud's phenomenon risk.
RESULTS
Analysis included 4743 individuals with Raynaud's phenomenon (mean age 58 years, 68% female) and 403,762 controls. There was no evidence of an effect of genetically mimicked beta-1-adrenoreceptor blockade on the risk of Raynaud's phenomenon, using systolic blood pressure (odds ratio = 0.93 per mmHg reduction; 95% confidence interval = [0.83, 1.04]; p = 0.19) or diastolic blood pressure (odds ratio = 0.91 per mmHg reduction; 95% confidence interval = [0.78, 1.05]; p = 0.19). The positive control exposure phosphodiesterase-5 inhibition was associated with reduced Raynaud's phenomenon risk.
CONCLUSIONS
We found no genetic evidence to support a causal association between beta-1-adrenoceptor blockade and Raynaud's phenomenon risk in either direction. Randomised controlled trials are required to confirm the safety of beta-1-adrenoceptor blockers in people with Raynaud's phenomenon.
引言/目的：雷诺现象是一种常见的血管痉挛性疾病，与健康相关生活质量下降有关，偶尔还会因病因导致缺血性组织损伤。β1肾上腺素能受体阻滞剂（如比索洛尔、阿替洛尔）对雷诺现象的影响尚不清楚。我们旨在评估基因模拟的β1肾上腺素能受体阻滞与雷诺现象风险之间的关联。
方法
我们利用基因中的两个蛋白质编码单核苷酸多态性，即rs1801252（A>G；Ser49Gly）和rs1801253（G>C；Arg389Gly），使用英国生物银行的个体水平数据，得出一个未加权的等位基因计数作为工具变量。雷诺现象使用国际疾病分类或Read编码进行定义。我们使用比率法，并分别以收缩压和舒张压作为生物标志物进行分析。为了检验这种方法和雷诺现象病例定义的有效性，我们还测试了磷酸二酯酶5抑制与雷诺现象风险之间的已知关联。
结果
分析纳入了4743例雷诺现象患者（平均年龄58岁，68%为女性）和403762名对照。使用收缩压（每降低1 mmHg的比值比=0.93；95%置信区间=[0.83, 1.04]；p=0.19）或舒张压（每降低1 mmHg的比值比=0.91；95%置信区间=[0.78, 1.05]；p=0.19）时，没有证据表明基因模拟的β1肾上腺素能受体阻滞对雷诺现象风险有影响。阳性对照暴露磷酸二酯酶5抑制与雷诺现象风险降低有关。
结论
我们没有发现遗传证据支持β1肾上腺素能受体阻滞与雷诺现象风险之间存在因果关联。需要进行随机对照试验来确认β1肾上腺素能受体阻滞剂在雷诺现象患者中的安全性。
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