高血压合并阻塞性睡眠呼吸暂停综合征患者代谢紊乱、靶器官损害情况及其与MK2基因的关联分析

发布时间：2018-03-19 18:55

本文选题：阻塞性睡眠呼吸暂停综合征　切入点：高血压　出处：《新疆医科大学》2013年博士论文　论文类型：学位论文

【摘要】：目的：阻塞性睡眠呼吸暂停低通气综合征（OSAS）在成年人中的患病率约为4%，临床以夜间反复发作的上气道阻塞，伴有血氧饱和度的降低，并由此引起白天嗜睡为特征。越来越多的临床和基础研究的证据表明，OSAS可能是多种心血管疾病和代谢性疾病的危险因素，如高血压、心力衰竭、心律失常、脂质代谢紊乱和糖尿病等。OSAS还可能导致或加速多器官功能损害，如左心室重构和功能损害、血管内皮损伤、脂肪肝、脑卒中和冠心病等。因此，有人认为OSAS应该成为新的心血管危险因素，或成为代谢综合征的一部分。OSAS对人类健康和生活质量的威胁不容小觑。了解OSAS患病人群特点，，与代谢紊乱及心血管疾病的关系，阐明OSAS引起的靶器官损害或加速已有疾病靶器官损害情况，对于预防和减轻OSAS及其对健康的负面影响有重要意义。另外，OSAS是多基因多因素的复杂疾病，其发病与遗传易感性相关，当具备遗传易感性时，与环境因素相互作用导致疾病的发生。明确OSAS发病的遗传背景对与治疗和预防都有积极意义。炎症一直被认为是OSAS发病的重要因素之一，大量的研究证明，炎症因子特别是肿瘤坏死因子与OSAS的发生密切相关。MK2基因是肿瘤坏死因子a重要的调节基因。本研究对2244例高血压合并OSAS患者进行了的临床资料的分析，明确其心血管危险因素聚集情况，与代谢紊乱的关系及靶器官损害情况，并选择炎症相关的基因MK2基因作为候选基因，探索其与OSAS发生的关系。方法：（1）入选研究对象共2244例，女性554例，男性1690例。根据睡眠呼吸紊乱指数（AHI)进行分组，分为单纯高血压组（473例），高血压合并OSAS组1772例，根据严重程度进一步分为轻度、中度和重度OSAS三个亚组（高血压合并轻度OSAS组649例，5"fA HI15次/小时；高血压合并中度OSAS组492例，15"fA HI30次/小时；重度OSAS组631例,AHI"g30次/小时）；（2）单因素方差分析或卡方检验比较四组间心血管危险因素聚集情况及代谢紊乱检出率。采用线性回归分析OSAS与胰岛素抵抗、胰岛β细胞功能和靶器官损害参数的关系。（3）采用TaqMan RT-PCR对896例OSAS患者DNA样本进行MK2基因型鉴定（rs4844550和1119385)。采用单因素方差分析和多重线性回归分析，观察rs4844550和1119385位点与睡眠质量相关参数的关系。结果：（1）OSAS人群的吸烟、脂质代谢紊乱、超重或肥胖、和2型糖尿病等心血管传统危险因素在高血压合并OSAS人群中的检出率显著高于单纯高血压人群（P0.05)，且检出率随OSAS严重程度的增加而增加；心血管危险因素聚集数目与OSAS严重程度呈正比(P0.05)，尤其与夜间血氧饱和度相关；（2）高血压合并OSAS患者糖代谢紊乱检出率高于单纯高血压组（P0.05)反应胰岛素敏感性的Matsuda指数、HOMA-IR指数与睡眠呼吸紊乱指数相关（P0.05)；饮酒与Matsuda指数、HOMA-IR指数和葡萄糖处置指数相关；（3）高血压合并OSAS患者向心性肥厚检出率显著高于不合并OSAS的高血压患者，即OSAS是高血压患者左心室肥厚的危险因素；OSAS的严重程度（AHI和/或夜间平均血氧饱和度）是心室结构损害和心脏舒张功能损害的危险因素(P0.05)；高血压合并OSAS患者的颈动脉斑块形成检出率显著高于单纯高血压人群； AHI与颈动脉内膜中层厚度相关；（4）MK2基因的rs11119385位点G等位基因与OSAS患者的阻塞性快眼睡眠总数、阻塞性睡眠紊乱指数和觉醒指数的增加显著相关；rs4844550位点A等位基因与OSAS患者的阻塞性快眼睡眠总数和阻塞性睡眠紊乱指数的增加相关。结论：（1）高血压合并OSAS的患者具有更严重的心血管危险因素聚集倾向；（2）OSAS增加了高血压患者胰岛素抵抗的风险；（3）OSAS加重了高血压患者的心脏损害和经动脉粥样硬化的发生；（4）MK2基因的rs4844550和rs11119385是OSAS患者睡眠质量下降的独立危险因素。
[Abstract]:Objective: obstructive sleep apnea hypopnea syndrome (OSAS) in the adult prevalence rate is about 4%, upper airway obstruction at night clinical recurrent, associated with decreased oxygen saturation, and the cause of daytime sleepiness. Clinical and basic research more and more evidence that OSAS may be a risk a variety of factors, cardiovascular diseases and metabolic diseases such as hypertension, heart failure, arrhythmia, lipid metabolic disorder and diabetes may also lead to accelerated.OSAS or multiple organ dysfunction, such as left ventricular remodeling and function damage, vascular endothelial injury, fatty liver, stroke and coronary heart disease. Therefore, some people think that OSAS should become new cardiovascular risk factors, metabolic syndrome or become a part of the.OSAS threat to human health and quality of life should not be underestimated. Understand the OSAS prevalence and characteristics of metabolic disorders and heart. The relationship between vascular disease, clarify the target organ damage caused by OSAS or accelerate the existing disease situation of target organ damage, have important significance to prevent and decrease the negative effect of OSAS and its health. In addition, OSAS is a complex multifactorial disease gene, its pathogenesis and genetic susceptibility, with genetic susceptibility and environmental factors. The interaction leads to the occurrence of the disease. The pathogenesis of clear genetic background of OSAS has positive significance and the prevention and treatment of inflammation. Has been considered an important factor in the pathogenesis of OSAS, a large number of studies have shown that inflammatory cytokines especially tumor necrosis factor and OSAS is closely related to the occurrence of tumor necrosis factor.MK2 gene is an important regulatory gene a analysis of the clinical data of 2244 cases of patients with hypertension and OSAS were the clear clustering of cardiovascular risk factors, and related metabolic disorders and The target organ damage, and inflammation related gene MK2 gene as candidate gene, and to explore the relationship of the occurrence of OSAS. Methods: (1) subjects, a total of 2244 cases, female 554 cases, male 1690 cases. According to apnea hypopnea index (AHI) were divided into simple hypertension group (473 Cases), hypertension and 1772 cases of OSAS group, according to the severity was further divided into mild, moderate and severe OSAS three subgroups (hypertension and mild OSAS group 649 cases, 5 "fA HI15 / h; hypertensive patients with moderate OSAS group 492 cases, 15 fA HI30 per hour; severe OSAS group 631 example, AHI" G30 times per hour); (2) the detection rate of single factor variance analysis and chi square test were compared between the four groups of cardiovascular risk factors clustering and metabolic disorders. By using the linear regression analysis of OSAS and the relationship between insulin resistance and beta cell function and target organ damage parameters. (3) by TaqMan R The T-PCR MK2 genotype in 896 patients with OSAS DNA samples (rs4844550 and 1119385). One way ANOVA and multiple linear regression analysis, the relationship between the relevant parameters observed in rs4844550 and 1119385 sites with sleep quality. Results: (1) OSAS population smoking, lipid metabolic disorder, overweight or obese, and 2 diabetes and other traditional cardiovascular risk factors in hypertension and the detection rate of OSAS in the crowd was significantly higher than that of simple hypertension group (P0.05), and the detection rate increased with the severity of OSAS increased; the clustering of cardiovascular risk factors and the severity of OSAS was proportional to the number (P0.05), especially with nocturnal oxygen saturation; (2) metabolic disorder in patients with hypertension complicated with OSAS glucose detection rate higher than the pure hypertension group (P0.05) insulin sensitivity reaction Matsuda index, HOMA-IR index and sleep apnea hypopnea index (P0.05) related to drinking and M; Atsuda index, HOMA-IR index and glucose disposition index; (3) the detection rate of hypertension combined with OSAS patients with concentric hypertrophy was significantly higher than that in patients with hypertension complicated with OSAS, OSAS is a risk factor for left ventricular hypertrophy in patients with essential hypertension; the severity of OSAS (AHI and / or night average oxygen saturation) were risk factors of ventricular structure damage and diastolic function damage (P0.05); carotid atherosclerosis in patients with hypertension and the formation of the OSAS detection rate was significantly higher than that of simple hypertension; AHI and carotid intima-media thickness; (4) obstructive rs11119385 allele G and OSAS of the MK2 gene in patients with rapid eye sleep total obstructive sleep hypopnea index the increase was significantly correlated with the arousal index increased; obstructive rs4844550 A allele and OSAS in patients with rapid eye sleep and total obstructive sleep hypopnea index. . conclusion: (1) OSAS patients with hypertension and cardiovascular risk factors clustering more serious tendency; (2) OSAS increased the risk of insulin resistance in patients with hypertension; (3) OSAS aggravate heart damage in patients with hypertension and atherosclerosis; (4) MK2 gene rs4844550 and rs11119385 are independent risk factors decreased sleep quality in patients with OSAS.

【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R544.1;R766

【相似文献】