Bartels Nina K, Börgel Jan, Wieczorek Stefan, Büchner Nikolaus, Hanefeld Christoph, Bulut Daniel, Mügge Andreas, Rump Lars C, Sanner Bernd M, Epplen Jörg T
Human Genetics, Ruhr-University Bochum, Germany.
BMC Med. 2007 Jan 1;5:1. doi: 10.1186/1741-7015-5-1.
The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent.
We investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/- 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the beta2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes.
Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023).
Our study showed no significant modifying effect of the functionally relevant beta2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.
阻塞性睡眠呼吸暂停（OSA）患者交感神经活动增强在很大程度上导致了动脉高血压的高患病率，并且提示这会对这些患者的甘油三酯和高密度脂蛋白（HDL）胆固醇水平产生不利影响。先前的研究表明，β2-肾上腺素能受体的功能相关多态性（Arg-47Cys/Arg16Gly和Gln27Glu）对这些危险因素有调节作用，但结果并不一致。
我们调查了一组429例患者（年龄55±10.7岁；男性361例，女性68例），这些患者患有中度至重度阻塞性睡眠呼吸暂停（呼吸暂停/低通气指数（AHI）为29.1±23.1次/小时），且平均具有较高的心血管疾病风险特征（体重指数31.1±5.6，60.1%的患者患有高血压，49.2%的患者患有血脂异常，17.2%的患者患有糖尿病）。我们对β2-肾上腺素能受体多态性进行基因分型，并研究了五种最常见的单倍型对OSA引起的血压、心率和血脂水平变化的调节作用。比较了不同基因型和单倍型之间心血管危险因素、冠心病（n = 55，12.8%）和存活心肌梗死（n = 27，6.3%）的患病率。
多变量线性/逻辑回归显示，AHI对日间收缩压和舒张压、心率、高血压患病率以及甘油三酯和HDL水平有显著且独立的（不受体重指数、年龄、性别、糖尿病的存在、抗糖尿病、降脂和抗高血压药物使用的影响）影响。β2-肾上腺素能受体基因型和单倍型对这些关系或血脂异常、糖尿病和冠心病的患病率没有调节作用，然而，对于所有三种多态性，杂合子携带者发生心肌梗死的相对风险显著较低（Arg-47Cys：n = 195，比值比（OR）= 0.32，P = 0.012；Arg16Gly：n = 197，OR = 0.39，P = 0.031；Gln27Glu：OR = 0.37，P = 0.023）。最常见单倍型（n = 113）（单倍型1；所有三种多态性均为杂合子）的携带者存活心肌梗死的患病率低五倍（OR = 0.21，P = 0.023）。
我们的研究表明，功能相关的β2-肾上腺素能受体多态性对OSA引起的血压、心率或血脂变化没有显著的调节作用。然而，在这组平均具有较高心血管疾病风险特征的人群中，这些多态性的杂合性与存活心肌梗死的较低患病率相关。
