Respiratory Diseases Research Unit, IRB Lleida, Lleida, Spain.
Sleep Breath. 2011 Sep;15(3):403-8. doi: 10.1007/s11325-010-0348-1. Epub 2010 Apr 21.
Obstructive sleep apnea syndrome (OSAS) is a complex disease with a strong genetic basis. One of the primary molecular domains affected by OSAS is sympathetic activity. Neuropeptide S (NPS) plays an important role in the regulation of the sleep-wakefulness cycle, anxiety states, and daytime sleepiness. It is important to study neuropeptides related to sympathetic activity regulation and how their function could be modified by genetic variants affecting the expression of these molecules.
We investigated the association of the non-synonymous polymorphism rs4751440 in the NPS precursor gene with OSAS and certain variables related to OSAS (daytime sleepiness, body mass index (BMI), insulin resistance, and blood pressure). This polymorphism causes an amino acid substitution in exon 3 of the human NPS precursor gene.
We included 253 OSAS patients and 70 healthy subjects. Genotyping was done by polymerase chain reaction using specific flanking primers and agarose gel electrophoresis. Daytime sleepiness, BMI, plasma levels of high-density lipoprotein, glucose, total cholesterol, insulin, triglycerides, and the homeostasis model assessment index were also determined.
A similar genotypic and allelic distribution was found in OSAS patients and controls. The risk of OSAS was not associated with the rs4751440 polymorphism. There was no significant interaction between daytime sleepiness or metabolic variables and the rs4751440 polymorphism.
Genotypic and allelic frequency distribution of the rs4751440 polymorphism was similar in OSAS patients and controls. In this population-based study, we could not show a significant association between rs4751440 polymorphism and susceptibility to OSAS or certain phenotypes related to OSAS (daytime sleepiness, BMI, systolic blood pressure, and insulin resistance) with the exception of diastolic blood pressure.
阻塞性睡眠呼吸暂停综合征（OSAS）是一种具有强烈遗传基础的复杂疾病。受 OSAS 影响的主要分子域之一是交感神经活动。神经肽 S（NPS）在调节睡眠-觉醒周期、焦虑状态和白天嗜睡方面发挥着重要作用。研究与交感神经活动调节相关的神经肽以及遗传变异如何影响这些分子的表达从而改变其功能非常重要。
我们研究了 NPS 前体基因中的非 synonymous 多态性 rs4751440 与 OSAS 以及与 OSAS 相关的某些变量（白天嗜睡、体重指数（BMI）、胰岛素抵抗和血压）之间的关联。该多态性导致人类 NPS 前体基因外显子 3 中的一个氨基酸取代。
我们纳入了 253 名 OSAS 患者和 70 名健康对照者。通过聚合酶链反应使用特定的侧翼引物和琼脂糖凝胶电泳进行基因分型。还测定了白天嗜睡、BMI、高密度脂蛋白、血糖、总胆固醇、胰岛素、甘油三酯和稳态模型评估指数。
OSAS 患者和对照组的基因型和等位基因分布相似。OSAS 的风险与 rs4751440 多态性无关。日间嗜睡或代谢变量与 rs4751440 多态性之间没有显著的相互作用。
rs4751440 多态性的基因型和等位基因频率分布在 OSAS 患者和对照组中相似。在这项基于人群的研究中，我们未能显示 rs4751440 多态性与 OSAS 的易感性或与 OSAS 相关的某些表型（白天嗜睡、BMI、收缩压和胰岛素抵抗）之间存在显著关联，但与舒张压除外。
