西北燥证与新疆地区代谢综合征相关性及其与PPARs基因多态性关系的研究

The Previous epidemiological survey on the Northwest Dryness Syndrome (NDS), which is completed by our research group during 2003-2010, indicated that NDS caused by dryness evil is the common disease status that influenced people's health of all ethnic groups lived in Xinjiang and Northwest region of China. In the meantime, it is also the possible risk factor of metabolic Syndrome, a frequently-occurring diseaseand in Xinjiang Uygur Autonomous Region. However, there is no support of clinical epidemiological data and material base on the relationship between the NDS and metabolic syndrome. On the basis of the previous research, applying the method of case-control study and mathematical statistics, this project intends to make a deep analysis on the correlation between the state of illness of metabolic syndrome and the main and accompanying syndromes of NDS. and gain the related clinical data. Furthermore, by means of molecular biology, PPARs gene polymorphisms is selected as the starting point of the molecular biology research on the relationship between the NDS and metabolic syndrome to reveal the influence of NDS on the metabolic syndrome and its process of components of individual susceptibility gene polymorphism. Thus an accurate and quantificational evaluation on the percentage of the NDS in causing disease and having the true risk exposure can be made to achieve the ultimate purpose of prevention against diseases by early intervening treatment and controlling exposure factors. This research will provide scientific basis for the formulating of prevention and cure strategy in Xinjiang Uygur Autonomous Region from the angle of "treating different diseases with the same therapy" in TCM. It is the deepening and innovationIn on the the basis of original research.

本课题组前期对于西北燥证流行病学研究证实，燥邪引发的西北燥证是影响新疆和西北地区各族居民身体健康的共同病证状态，同时也是代谢综合症这个新疆多发病可能的危险因素。但尚缺乏临床流行病学数据及相关物质基础支持。在继往研究基础上，本项目首先运用病例对照设计及诸多数理统计分析方法，开展西北燥证与代谢综合征相关性研究，以获取西北燥证与新疆地区代谢综合征罹患关系的临床数据；并进一步创新性借助分子生物学手段，以PPARs基因多态性作为西北燥证与代谢综合征关系分子的切入点，揭示西北燥证对代谢综合征及其各组份个体易感性基因多态性发病过程的影响，准确、定量地对西北燥证在引起疾病和具有真实暴露危险度中所占的份额作出评价，以便通过早期干预、有效调控暴露因素达到预防疾病的目的。本项研究为中医从"异病同治"角度制定新疆地区代谢综合征防治策略提供科学依据，是在原有工作基础上的深化和创新。

本课题以PPARs基因态性作为西北燥证与代谢综合征关系分子的切入点，揭示西北燥证对代谢个体易感基因多态性发病过程的影响。项目的主要研究内容有：1.西北燥证易感体质Logistic回归分析；2.新疆喀什地区代谢综合征与西北燥证病例对照研究；3.西北燥证与PPARƳ基因多态性关系的研究；4.西北燥证患者Th17/Treg细胞免疫失衡研究。.项目获得的重要结果：(1)阴虚体质罹患西北燥证的风险为非阴虚体质者的2.43倍(95%CI 1.541～3.831)。肝虚体质罹患西北燥证的风险为非肝虚者的5.264倍（95%CI 2.066～13.413）。(2)多因素Logistic回归分析结果,吸烟史、饮酒史、嗜食肥甘及高血压均进入回归模型,其OR值分别为3.945、4.334、0.370、2.142,均P＜0.01。(3)喀什地区病例组西北燥证罹患率（55%），高于对照组（38.83%）（ =14.304，P<0.01）。(4)西北燥证组CC基因型频率高于对照组，其余位点基因分型在两组间未显示出统计学差异。少见等位基因频率比较，西北燥证组低于对照组（p<0.01）。多因素Logistic回归分析显示，年龄在＞30～45岁、45～55岁之间患西北燥证的风险分别是其他年龄段的1.796倍与1.561倍。CC基因型患西北燥证的风险是CT/TT基因型的0.524倍。 (5)西北燥证组IL-17A、IL-10含量分别为（23.63±2.81）pg/ml和（3.00±1.61）pg/ml，对照组IL-17A、IL-10含量分别为（16.14±1.85）pg/ml和（1.60±0.24）pg/ml，P<0.01。(6)西北燥证组中TNF-α、INF-γ含量分别为（5.25±3.43）pg/ml、（1.59±1.79）pg/ml。健康对照组TNF-α、INF-γ含量分别为（2.35±3.48）pg/ml、（2.52±1.90）pg/ml, P＜0.01。.本项目的科学意义是：(1)西北燥证易感体质为阴虚、肝虚。(2)代谢综合征患者中嗜食肥甘及喜辣、喜咸者,建议适当调整饮食口味,增加酸味饮食,荤素搭配,戒烟酒,控制血压,可能有助于适应当地气候、生活环境,减少西北燥证的发生。(3)PPARƳ基因rs2921190多态性与西北燥证易感性相关。(4) 西北燥证患者存在Treg/Th17免疫失衡。