Winker R, Barth A, Valic E, Maier R, Osterode W, Pilger A, Rüdiger H W
Division of Occupational Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Int Arch Occup Environ Health. 2005 Apr;78(3):171-7. doi: 10.1007/s00420-005-0605-y. Epub 2005 Feb 18.
Idiopathic orthostatic intolerance (IOI) is a common disorder that is characterized by chronic orthostatic symptoms and substantial increases in heart rate and plasma norepinephrine concentrations that are disproportionately high while standing. Several features of the syndrome, including the tachycardia, tremulousness, and exaggerated norepinephrine have been considered potentially due to hypoactive or hyperactive states of adrenergic receptors of the sympathetic nervous system. The aim of this study was therefore to ascertain whether genotypes at eight polymorphic loci within five relevant adrenergic receptor genes (alpha2A, alpha2B, alpha2C, beta1 and beta2) influence the risk for IOI.
We studied 80 young men in military service (20 patients with IOI and 60 age-matched controls). All participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. Genotyping at the eight loci (alpha2ALys251, alpha2BDel301-303, alpha2CDel322-325, beta1Gly49, beta1Arg389, beta2Arg16, beta2Glu27, beta2Ile164) was performed in all participants. Chi-square tests of independence were used to test for associations between IOI and genotype. In addition, an association of the polymorphisms with haemodynamic variables (heart rate, supine and upright blood pressure) was ascertained using one-way variance analysis.
For the beta1Gly49 polymorphism we found a decrease in the risk of IOI among persons who were homozygous (odds ratio, 0.88; 95% confidence interval, 0.81-0.97). In addition, we found an association between beta1Gly49 and decreased heart rate in the upright position, regardless of IOI diagnosis. There were no associations with the other studied polymorphisms and IOI.
Our current results suggest that the beta1Gly49 polymorphism is protective for IOI. This is likely one of several common genetic loci that may represent modifiers of IOI phenotypes.
特发性直立性不耐受（IOI）是一种常见疾病，其特征为慢性直立性症状，以及站立时心率和血浆去甲肾上腺素浓度大幅升高，且升高幅度不成比例。该综合征的几个特征，包括心动过速、震颤和去甲肾上腺素过度分泌，被认为可能是由于交感神经系统肾上腺素能受体的低活性或高活性状态所致。因此，本研究的目的是确定五个相关肾上腺素能受体基因（α2A、α2B、α2C、β1和β2）内八个多态性位点的基因型是否会影响IOI的发病风险。
我们研究了80名年轻现役军人（20名IOI患者和60名年龄匹配的对照者）。所有参与者均接受了倾斜试验，包括在仰卧位和站立30分钟期间监测血压、心率和血浆儿茶酚胺。对所有参与者进行了八个位点（α2ALys251、α2BDel301 - 303、α2CDel322 - 325、β1Gly49、β1Arg389、β2Arg16、β2Glu27、β2Ile164）的基因分型。采用卡方独立性检验来检验IOI与基因型之间的关联。此外，使用单因素方差分析确定多态性与血流动力学变量（心率、仰卧位和直立位血压）之间的关联。
对于β1Gly49多态性，我们发现纯合子个体患IOI的风险降低（优势比，0.88；95%置信区间，0.81 - 0.97）。此外，无论IOI诊断如何，我们发现β1Gly49与直立位心率降低之间存在关联。其他研究的多态性与IOI之间无关联。
我们目前的结果表明，β1Gly49多态性对IOI具有保护作用。这可能是几个常见基因位点之一，可能代表IOI表型的修饰因子。
