Interdisciplinary Center of Sleep Medicine, Charité Universitaetsmedizin-Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Sleep Med. 2010 Feb;11(2):213-7. doi: 10.1016/j.sleep.2009.06.009. Epub 2010 Jan 18.
Traits of obstructive sleep apnea syndrome (OSAS) such as impaired ventilatory control, craniofacial abnormalities, and concomitant cardiovascular diseases are associated with modified endothelin-1 gene (EDN-1) or endothelin-receptor-subtype-a (EDNRA) gene. The endothelin system regulates the cardiovascular homeostasis. EDN-1 interacts mainly with EDNRA for signal transduction. In our study we investigate associations of EDNRA-polymorphisms (four frequent polymorphisms with an allele frequency >5%) and OSAS severity.
Three hundred ninety-three patients older than 18years, of Caucasian origin and with OSAS (AHI>5/h and daytime sleepiness) were investigated by cardiorespiratory polysomnography. In addition 58 control subjects with healthy sleep were recruited from nearly 300 volunteers. We analysed the EDNRA-polymorphisms E335E, H323H, G-231A and G+70C by polymerase-chain-reaction, restriction-fragment-length-polymorphism and real-time-PCR.
Carrier of the mutant G-231A allele had a significantly lower AHI (p=0.03, OR 0.53, 95% CI 0.3-0.94) when comparing patients and controls. When comparing OSAS severity groups without controls we could not detect significant correlations for the four investigated EDNRA-polymorphisms. Our data confirm that BMI (p<0.001) and male gender (p=0.02) are significantly associated with AHI. The allele frequencies were similar.
The genetic investigation of OSA remains important. Our control group was relatively small and we investigated 4 reasonable candidates out of more than 100 EDNRA-polymorphisms. The detected protective effect of the mutant G-231A allele needs further confirmation. Gene based research in OSAS should use genome wide scan and should still consider the endothelin system.
阻塞性睡眠呼吸暂停综合征（OSAS）的特征，如通气控制受损、颅面异常和并发心血管疾病，与内皮素-1 基因（EDN-1）或内皮素受体亚型-a（EDNRA）基因的改变有关。内皮素系统调节心血管稳态。EDN-1 主要通过 EDNRA 进行信号转导。在我们的研究中，我们研究了 EDNRA 多态性（四个常见的多态性等位基因频率>5%）与 OSAS 严重程度的相关性。
研究了 393 名年龄在 18 岁以上、白种人、有 OSAS（AHI>5/h 和白天嗜睡）的患者，通过心肺多导睡眠图进行检查。此外，从近 300 名志愿者中招募了 58 名睡眠健康的对照者。我们通过聚合酶链反应、限制性片段长度多态性和实时 PCR 分析了 EDNRA 多态性 E335E、H323H、G-231A 和 G+70C。
与对照组相比，携带突变 G-231A 等位基因的患者 AHI 显著降低（p=0.03，OR 0.53，95%CI 0.3-0.94）。在比较无对照组的 OSAS 严重程度组时，我们无法检测到四个研究的 EDNRA 多态性的显著相关性。我们的数据证实 BMI（p<0.001）和男性（p=0.02）与 AHI 显著相关。等位基因频率相似。
OSA 的遗传研究仍然很重要。我们的对照组相对较小，我们从 100 多个 EDNRA 多态性中研究了 4 个合理的候选基因。突变 G-231A 等位基因的保护作用需要进一步证实。OSAS 的基因研究应使用全基因组扫描，并仍应考虑内皮素系统。
