云南少数民族地中海贫血的遗传多样性及常见基因突变型适应机制的研究

Our previous study has found that thalassemias (thal for shot) are a group of hereditary disorders shared the highest incidence in Yunnan province, with the detection rate of suffers and carriers up to 22% among the minorities living in southern areas to the Tropic of Cancer in Yunnan. The study showed that more diversities of gene mutations were found compared to the populations in other areas of the country, and the gene mutantion types obviously had geographical features in Yunnan residents. Based on the field work, this project will analyze gene frequencies of common mutations such as - - SEA、-α3.7、CD26(G→A)、CD17(A→T)、CD41/42(-CTTT) systematically, via detecting the diversities of goblin genes among the minorities and Han ethnic groups living in southern and southwestern of Yunnan province. To explore the differences on some critical health indicators including the incidences of associated complications, malaria mortality rates, and average life expectancy between families with and without mutants such as - - SEA, βE and so on, the health status of 150 selected families with thal patients carrying such mutants as well as the control families without thal living in same areas will be studied through a transect investigation of 3-year follow up. The spectrum of complications in thal patients and carriers as well as its influences on the henogenesis and average life expectancy will also be studied in this project. The adaptation mechanism of these gene mutation types under the selection pressure of specific geographical, climatic environment and related diseases might be elucidated by the project.

课题组前期研究发现地中海贫血（地贫）是云南省发病率最高的遗传病，患者和携带者的检出率在北回归线以南少数民族中高达22%以上，基因突变的多样性比国内其它地区人群更加丰富，基因突变型有明显的地理特征。本项目拟以现场人群为基础，通过检测云南南部、西南部少数民族和汉族孕产妇的珠蛋白基因多样性，系统地分析这些地区少数民族中珠蛋白基因- - SEA、-α3.7、CD26(G→A)、CD17(A→T)、CD41/42(-CTTT)等常见突变型的基因频率；对150个常见突变型患者和携带者家系的成员进行3年的横断面跟踪调查，与当地无地贫的家系相对照，研究- - SEA和βE等常见突变型携带者和患者在相关并发症发生率、疟疾病死率、人均期望寿命等重要健康指标上的差异，认识云南常见基因突变型地贫患者和携带者的常见并发症以及对个体发育和期望寿命的影响，阐明在特定地理气候环境和相关疾病选择压力下这些基因突变型的适应机制。

完成云南省基层医务人员地中海贫血（地贫）防控知识培训800人次，专业进修120人次，构建了全省地贫防控工作体系和本项目的基层合作网络。项目完成云南省约9万名受检者的地贫流行调查，全省地贫携带率平均9.73%，西南边境地区地贫携带率较高，东北部和中部较低；云南省地贫基因突变种类占全国所发现地贫基因突变的一半以上，Hb E携带率在全国最高。地贫携带率较高的民族依次为傣族（29.0%）、傈傈族（26.7%）、壮族（25.0%）、回族（13.4%）；筛查阳性率较高的地区依次为德宏州（25.0%）、西双版纳州（21.7%）和文山州（20.1%）。全省β地贫多于α地贫，在云南东南部地区β-地贫最常见的突变类型是CD41-42，而云南西南部地区最常见的类型是CD26（即Hb E）。帮助文山州、德宏州、西双版纳州、红河州和临沧市建立了州市级地贫筛和贫血儿童转诊服务体系。通过该项目研究，对云南地贫基因突变特点和复杂性有了进一步认识，制定了符合云南地贫防控需要的筛查诊断工作流程图和技术指标。参与和主持制定了2部国家卫生计生委的地贫防控相关技术规范和标准，已经发表研究论文11篇，其中SCI论文3篇，累计影响因子>9；另外还有1篇SCI论文已经被接受，正在出版，单篇影响因子7.7。超额完成了本项目预定目标。

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