西藏地区人群大骨节病分子流行病学研究

Kashin-Beck disease (KBD) is a special type of endemic disease of bone and joint deformities, which is seriously endangering the population health conditions in Tibet and other regions, its prevention task is arduous and its etiology remains unclear. Our previous studies showed that the occurrence of KBD is the result of interaction between environmental factors and genetic factors. At present, Tibet, as one of KBD high-risk areas in China, has not yet been carried out the genome-wide research on genetic and environmental factors in the pathogenesis of different genetic backgrounds. This research intends to screen genome-wide single nucleotide polymorphism (SNP) and copy number variation (CNV) genetic markers in Tibet KBD patient group through the use of Illumina chip technology, and verifies the chip testing results in large sample populations by utilizing Sequenom SNP genotyping technologies and Real Time PCR technology, further to analyze the interaction between the environment and genes which would affect the occurrence of KBD and its impact on the degree of illness. The project will eventually establish kashin-beck disease risk assessment model in Tibet area, establish foundation for subsequent implementation kaschin-beck disease screening of high-risk population and molecular diagnosis method, and offer a new research idea for other local disease prevention in Tibet.

大骨节病（Kashin-Beck disease, KBD）是一种特殊类型的地方性骨关节畸形病，严重危害西藏等地区的人口健康，防治任务艰巨，至今病因不明。本课题组的前期研究表明，大骨节病的发生是环境因素与遗传因素相互作用的结果。目前，在我国大骨节病高发地区之一西藏尚未开展基于全基因组范围的基因与环境因素在不同遗传背景人群中的发病机制研究。本课题组拟采用Illumina芯片技术对西藏地区大骨节病人群全基因组单核苷酸多态性（SNP)与拷贝数变异(CNV)遗传标记进行筛查，并利用Sequenom SNP分型技术和Real Time PCR技术在大样本人群中对芯片结果进行验证，进一步分析环境与基因相互作用导致大骨节病发生及对患病程度的影响。本项目最终将建立西藏地区大骨节病患病风险评估模型，为后续实施大骨节病高危人群的筛查及分子诊疗方法的建立奠定基础，同时为西藏其它地方性疾病防治提供新的研究思路。

大骨节病（Kashin-Beck disease, KBD）是一种特殊类型的地方性骨关节畸形病，严重危害西藏等地区的人口健康，防治任务艰巨，至今病因不明。本课题组的前期研究表明，大骨节病的发生是环境因素与遗传因素相互作用的结果。目前，在我国大骨节病高发地区之一西藏尚未开展基于全基因组范围的基因与环境因素在不同遗传背景人群中的发病机制研究。本课题组拟采用Illumina芯片技术对西藏地区大骨节病人群全基因组单核苷酸多态性（SNP)与拷贝数变异(CNV)遗传标记进行筛查，并利用Sequenom SNP分型技术和Real Time PCR技术在大样本人群中对芯片结果进行验证，进一步分析环境与基因相互作用导致大骨节病发生及对患病程度的影响。最终发现rs1965214（ABI3BP）、rs3806093（COL9A1）、rs1352815（CD2AP）、rs1388382（CD2AP）和rs11048526（CD2AP）与藏族人群大骨节病风险增加显著相关。性别分层分析显示rs1388382（CD2AP）、rs694155（CD2AP）和rs694155（CD2AP）与藏族女性人群的大骨节病患病风险增加显著相关；rs1139793（TXNRD2）与藏族女性人群的大骨节病患病风险降低显著相关。拷贝数变异CNV452位于3q12.2染色体（hg18）的100,690,157bp至100,691,151bp。CNV452与大骨节病患病风险也显著相关。该研究结果为后续实施大骨节病高危人群的筛查及分子诊疗方法的建立奠定基础，同时为西藏其它地方性疾病防治提供新的研究思路。