【作者】 唐芸；

【导师】 王洪琦；

【作者基本信息】 广州中医药大学 ， 中医基础理论， 2009， 博士

【摘要】 研究目的探讨HLA基因多态性与广东汉族人群湿热证候易感性的相关性,同时探索广东汉族人群湿热体质形成的部分相关影响因素。针对特定的种群,以相对稳定的体质为纲来研究证候的遗传学基础,更有利于对证候本质研究的深入,同时也为“异病同证”的机制探讨提供新的视角。研究方法1.采用横断面现场调查方法对148名18岁以上的广东籍汉族人群实施问卷调查,其中湿热体质组65例,非湿热体质组83例,重点了解湿热体质人群的饮食生活习惯、社会人口学情况;制定湿热体质量表及湿热体质诊断标准并进行湿热体质评分;应用单因素分析和多元逐步回归分析法对部分相关影响因素进行分析。2.采用基因芯片分型技术分别对广东籍和非广东籍的湿热体质、正常质人群各15例进行HLA-A、B及DRB1基因分型检测。直接计数法计算各组的HLA各等位基因的表型频率,两组之间等位基因的表型频率差异分析运用Fisher精确检验统计分析。研究结果1.按P＜0.10,多元逐步回归分析,入选了12个因素,按影响程度大小的排列是:年龄、喜烧烤、喜凉、嗜烟、喜甘甜、体质指数、喜肉类、早睡早起、喜咸鱼、喜辛辣、喜酸、睡眠不规律,其中喜凉、年龄偏大、喜烧烤、体质指数高、嗜烟、喜甘甜、喜肉类、喜咸鱼、睡眠不规律的人群湿热体质得分值较高,而早睡早起、喜酸、喜辛辣者湿热体质得分值相对偏低。2.广东籍湿热体质组HLA-A*02等位基因表型频率明显低于广东籍正常质组(26.7%vs 50.0%,P=0.006)。3.广东籍湿热体质组HLA-B*15、B*46等位基因表型频率显著低于非广东籍湿热体质组(3.3%vs 23.3%,P=0.035;3.3%vs 23.3%,P=0.035),B*40等位基因表型频率高于非广东籍湿热体质组(30.0%vs 16.7%)。4.与广东籍正常质组比较,广东籍湿热体质组B*40基因表型频率呈升高趋势(30.0%vs 16.7%),B*46、B*15、DRB1*09基因表型频率呈下降趋势(3.3%vs 20.0%;3.3%vs 16.7%;6.7%vs 16.7%)。与非广东籍正常质组比较,非广东籍湿热体质组A*11、B*46、DRB1*08表型频率呈升高趋势(33.3%vs 16.7%;23.3%vs 13.3%;20.0%vs 3.3%),而A*24、DRB1*09等位基因表型频率呈下降趋势(13.3%vs 30.0%;10.0%vs 23.3%)。研究结论1.广东籍湿热体质形成与喜食甘甜、肉类、内脏、生冷冻物、烧烤、咸鱼、嗜烟、睡眠不规律以及肥胖等后天饮食起居因素密切相关,我们需要重点进行饮食生活习惯的指导和健康教育宣传,提倡合理的饮食结构和习惯,培养科学的生活方式,改善调养湿热体质,以促进健康、预防疾病。2.提示HLA-A*02可能是广东籍湿热体质人群的保护性基因。3.提示广东籍湿热体质与非广东籍湿热体质人群可能存在不同的免疫遗传学基础。更多还原

【Abstract】 ObjectiveTo explore the correlation between HLA alleles polymorphism and the susceptibility of damp-heat syndrom,and to assess the related influencing factors of damp-heat constitution in Guangdong Ham’ s population.Study on the genetic basis of syndrome focussed on relatively stable constitution and to specific population,will help to research the essence of syndrome deeeply and provide a new angle to discusse the mechanism of." the same syndrome of different disease".Methods1.By using cross-sectional study method,148 Ham’ s people(over 18 years old,65 in damp-heat constitution group and 83 in normal group) in Guangdong province were investigated with questionaire to emphasize on the damp-heat constitution people’ s diet and lifestyle and the general demography.We drew up the diagnostic standards of damp-heat constitution and the damp-heat constitution in Chinese Medicine Questionaire,by which the scores of the damp-heat constitution were measured.Single factor analysis and multiple stepwise regression were applied to analyze major influencing factors.2.The genotypes of HLA-A,B and DRB1 alleles were determined in the damp-heat constitution and the normal constitution group come from Guangdong province and non-Guangdong province respectively(15 cases in each group) by DNA chips.The phenotype frequencies of HLA alleles in each group were calculated by direct counting method.Fisher’ s exact test was applied to analyze the diffrences of the phenotype frequencies of HLA alleles between two groups.Results1.As P<0.10,12 influencing factors entered into the regression equation by mutiple stepwise regression analysis,they were as follows in decreasing order:age,barbecue,cold drink,tobacco addiction,sweet food,body mass index(BMI),meat,sleeping early and getting up early,salted fish,spicy food, sour food,and irregular sleep.The scores of the damp-heat constitution were relatively higher in the individual prefered to cold drinking,barbecue,sweet food,meat,salted fish and smoking,elder,and the individual who having irregular sleep,while the scores were relatively lower in the individual who sleeping early and getting up early,and preferring to sour or spicy food.2.The phenotype frequency of HLA-A*02 in the damp-heat constitution group was lower than that in normal constitution group in Guangdong Han population(16.7%vs 50.0%,P=0.006).3.The phenotype frequencies of HLA-B*15,B*46 alleles in the damp-heat constitution group of the Han people in Guangdong were significantly lower than those in damp-heat constitution group in non-Guangdong Hans(3.3%vs 23.3%, P=0.035;3.3%vs 23.3%,P=0.035);the frequency of B*40 allele in the damp-heat constitution group of the Han people in Guangdong was higher than that of non-Guangdong Hans(30.0%vs 16.7%).4.Compared with the normal constitution group in Guangdong Han population,the phenotype frequencies of HLA-B*40 had tended upwards(30.0%vs 16.7%),while the phenotype frequencies of B*46、B*15、DRB1*09 had tended downwards(3.3%vs 20.0%;3.3%vs 16.7%;6.7%vs 16.7%) in the damp-heat constitution group of the Han people in Guangdong.Compared with the normal constitution group in non-Guangdong Han population,the phenotype frequencies of HLA-A*11、B*46、DRB1*08 had tended upwards(33.3%vs 16.7%;23.3%vs 13.3%; 20.0%vs 3.3%),while the phenotype frequencies of A*24、DRB1*09 had tended downwards(13.3%vs 30.0%;10.0%vs 23.3%)in the damp-heat constitution group of the Han people in non- Guangdong.Conclusion1.The eating habits of preferring to sweet food,meat,cold drinking, barbecue,salted fish and smoking,the living habits of irregular sleep,and obesity were the important factors in the development of damp-heat constitution in Guangdong Han population,lt is expectable to prevent the disease and promote the health via correting damp-heat constitution towards high-risk population by changing lifestyle and behavior.2.It suggests that HLA-A*02 might be the protective gene of damp-heat constitution in Guangdong Han population.3.The results indicate that there might be the different immunogenetics basis in the damp-heat constitution of Guangdong and non- Guangdong Han population.更多还原