阻塞性睡眠呼吸暂停低通气综合症（OSAHS）是人群中普遍存在的以睡眠通气不足、慢性间歇性缺氧、酸碱平衡紊乱为表现的一类疾病，发病机制不明，呼吸肌无力和中枢化学感受器反应性降低是其形成的重要原因。研究表明酸敏感钾离子通道TASK-1,TASK-3的表达量与OSAS的发生相关，但目前缺乏人群研究证据。项目旨在通过较大样本量的样本中对血液、尿液标本的PH值、K+水平等检测，明确钾离子水平与OSAS的相关性，同时针对TASK1/3基因功能区测序，选取代表性遗传多态性位点（TagSNPs），利用Taqman技术在大样本OSAHS人群中鉴定TagSNPs的基因型，并分析相关位点与疾病临床表型的相关性，为疾病治疗提供初步线索。

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disorders characterized with hypoventilation during sleep, chronic intermittent hypoxia and acid-base imbalance. Although the exact pathogenesis is unknown, the weakness of respiratory muscles and reduced reactivity of central chemical receptor are thought considered as important reasons. Studies have shown that the expression of acid-sensitive potassium channel (TASK-1 and TASK-3) was related to the occurrence of OSAS, but population-based studies as to TASK-1 and TASK-3 genes were lack. The present project aims to perform a population-based association study in a larger size sample to explore the correlation between PH value and K+ level of respiratory gas condensate, blood as well as urine specimen and final phenotypes of OSAHS. Simultaneously, according to sequencing in patients with severe OSAHS, the representative genetic variations (TagSNPs) were selected, then TaqMan-PCR is used to identify the genotypes of TagSNPs in TASK-1 and TASK-3 genes in a large population of OSAHS. Finally, the case-control study were conducted to explore the association between TagSNPs of TASK-1/3 genes and OSAHS related phenotypes, further the function of positive SNPs will be analyzed to confirm the potential targets for the treatment of disease.

睡眠呼吸暂停综合症（OSAS）以反复间歇性低氧和高碳酸血症为主要特点，是目前最常见的继发性高血压之一。目前发病机制仍不清楚。国内外相关细胞学和动物实验（小鼠模型、果蝇模型等）一致认为酸敏感钾离子通道1/3（TASK-1/3）基因表达与OSAS相关，但缺乏人群样本的研究数据。本项目纳入2016年4-12月就诊新疆自治区人民医院高血压中心年龄>18岁并完善多导联睡眠监测（PSG）的患者345名，重度OSAS者169名，非OSAS患者176名。（1）采集基线及生化指标，并提取受试对象外周血基因组DNA；（2）利用Hapmap等国际公共数据库选取TASK-1基因rs1275988和rs2586886位点，TASK-3基因rs2615374，rs3808403，rs888345作为标签SNPs。利用KASP方法对标签SNPs进行基因分型，分析TASK-1/3基因标签SNPs与OSAHS的相关性。研究发现：体重指数≥28kg/m2人群中，TASK-1基因rs1275988和rs2586886位点基因型、等位基因频率在重度OSAS和非OSAS两组间分布差异有统计学意义（基因型分布：P=0.034和P=0.025; 等位基因频率: P=0.007和P=0.002)。Logistic回归分析提示rs1275988和rs2586886是OSAS的保护性因素（OR值分别为0.340和0.283)。TASK-3基因rs2615374和rs3808403位点不同基因型(P分别为0.047，0.005)和rs2615374等位基因模型(P=0.014)在两组间分布频率不同。rs3808403位点CT+TT基因型是重度 OSAS的风险因素(OR=2.09, 95%CI: 1.16-3.78, P=0.014)。此外，年龄≥47岁，BMI，腹围及高甘油三酯水平等均为OSAS的风险因素。项目建立了OSAS人群TASK1/3基因遗传资源库，为今后研究奠定了一定基础。明确了TASK-1基因rs1275988和rs2586886可能是肥胖OSAS患者保护性遗传标记之一；TASK-3基因rs2615374和rs3808403位点与重度OSAS相关，rs3808403位点CT+TT基因型是重度OSAS的风险因素，为OSAHS发病机制探讨提供一定参考。