CTRP1及相关物质TNF-α、IL-1β、NGFIB、NURR1基因变异与睡眠呼吸暂停低通气综合征相关性高血压的关联研究

OSAHS-related hypertension is one of the most common resistant hypertension, to which the metabolic inflammation and excessive aldosterone secretion are suggested as the contributing factors. Complement C1q tumor necrosis factor related protein 1 (C1qTNF-related protein-1, CTRP1 ) is supposed to play a role in the pathogenesis of OSAHS-related hypertension due to its role in regulating the metabolic inflammation and aldosterone production. Besides, TNF alpha, beta- IL-1βand NGFIB, NURRA are key factors to the production and function of CTRP1. This study is designed to discuss the associations between CTRP1 and its related factors and OSAHS-related hypertension via comparing DNA, RNA and protein levels by case-control studies, including the detection of variants in CTRP1, TNF alpha, beta- IL-1βand NGFIB, NURRA genes, identification of genotypes by Taqman-PCR in general population, tests of the RNA and protein levels of CTRP1 and its related factors. On a whole, we intend to provide evidence for the further explanation to the mechanism of OSAHS-related hypertension.

OSAHS相关性高血压是一种最常见的抵抗性高血压。研究证实其发病机制可能与代谢性炎症及醛固酮分泌增多等有关。补体C1q肿瘤坏死因子相关蛋白1（C1qTNF-related protein-1，CTRP1）通过调节代谢性炎症及醛固酮的生成而可能成为OSAHS相关性高血压血压升高的重要调节物质。TNF-α、IL-1β及NGFIB、NURRA是调节CTRP1生成及使其发挥作用机制的重要物质。课题应用测序技术筛查CTRP1及TNF-α、IL-1β、NGFIB、NURRA基因变异位点，TaqMan-PCR技术在大样本人群中进行基因型鉴定，在小样本人群脂肪细胞检测CTRP1及其相关物质RNA及蛋白含量，通过病例-对照研究拟从DNA、RNA、蛋白质等不同水平探讨CTRP1及其相关物质与OSAHS相关性高血压的关系，为OSAHS相关性高血压今后的机制研究提供研究基础。

补体C1q肿瘤坏死因子相关蛋白1（C1q TNF-related protein-1， CTRP1）通过调节代谢性炎症及醛固酮的生成而可能成为OSAHS 相关性高血压血压升高的重要调节物质。TNF-α和IL-1β是调节CTRP1 生成及使其发挥作用机制的重要物质。本研究通过测序技术筛查 CTRP1及TNF-α、IL-1β基因变异位点，TaqMan-PCR技术在大样本人群中进行基因型鉴定， 分析了OSAHS相关性高血压的人群分布特征及发病特点，明确了基因变异在 OSAHS相关性高血压人群中的分布特征，明确人群代表性变异位点，为人类研究单核苷酸多态性（ single nucleotide polymor－phisms， SNP）奠定基础。在此基础上，评估了OSAHS患者与循环SPs的水平之间的关系及SPs用于临床OSA的诊断价值，验证了肥胖OSA患者的FRC较肥胖者显著下降的原因主要是肺的弹性回缩力增加或其倒数顺应性下降，用IOS测定的结果作为筛检工具，将OSAS患者从肥胖的打鼾者中区分出来的可能性进行预测。

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