Endothelial NO synthase polymorphisms and postural tachycardia syndrome
Endothelial NO synthase polymorphisms and postural tachycardia syndrome
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DOI：
10.1161/01.hyp.0000185462.08685.da
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发表时间：
2005-11-01
期刊：
影响因子：
8.3
通讯作者：
Robertson, D
中科院分区：
文献类型：
--
作者：
Garland, EM;Winker, R;Robertson, D
体位性心动过速综合征（POTS）是一种异质性疾病，其特征是心率过度升高和与直立位脑灌注不足一致的症状。由内皮NO合酶产生的NO是调节血流的重要因素。NO合酶亚型3基因启动子区（T-786 C）和外显子7（E298 D）的遗传多态性影响酶活性，并与许多心血管疾病相关。由于POTS中的一些发现提示NO介导的功能异常，我们推测这些多态性的变异基因型可能会增加发生POTS的风险，并与更严重的症状相关。我们对来自纳什维尔、田纳西州和奥地利维也纳的136名POTS患者（平均年龄32.2 ± 9.9岁; 46名男性和90名女性）进行了基因分型，并将他们与191名健康志愿者（平均年龄29.1 ± 8.0岁; 127名男性和64名女性）进行了比较。参与者还接受了直立测试，包括仰卧和直立时的血压、心率和血浆去甲肾上腺素测量。POTS患者中-786 CC和298 DD基因型的频率Z'显著低于对照组（-786 CC的比值比[OR]，0.28; 95%置信区间[CI]，0.14至0.57; P=0.001; 298 DD的比值比[OR]，0.44; 95% CI，0.21至0.91; P=0.033）。根据2位点基因型分析，-786 CC和298 EE或298 ED患者在站立时心率和血浆去甲肾上腺素变化最大。这些结果表明，NO可能影响POTS的发展和POTS症状的严重程度。
Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene affect enzyme activity and have been associated with a number of cardiovascular diseases. Because some findings in POTS suggest aberrant NO-mediated functions, we postulated that the variant genotypes of these polymorphisms may increase the risk of developing POTS and correlate with more severe symptoms. We genotyped 136 patients with POTS (mean age 32.2 +/- 9.9 years; 46 ,en and 90 women) from Nashville, Tenn, and Vienna, Austria, and compared them with 191 healthy volunteers (mean age 29.1 +/- 8.0 years; 127 men and 64 women). Participants also underwent orthostatic testing with blood pressure, heart rate, and plasma norepinephrine measurements while supine and upright. The frequencies of the -786CC and 298DD genotypes were significantly lower Z' in patients with POTS than in control subjects (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.14 to 0.57; P=0.001 for -786CC; and OR, 0.44; 95% Cl, 0.21 to 0.91; P=0.033 for 298DD). According to 2-locus genotype analyses, patients with -786CC and 298EE or 298ED experienced the largest changes in heart rate and plasma norepinephrine with standing. These results indicate that NO may influence the development of POTS and the severity of POTS symptoms.