中文摘要
本项目组在全基因组扫查中，经家系连锁分析将中国人2型糖尿病易感基因定位在1q区域，同时国际上多个独立研究也将2型糖尿病易感基因定位在该区段。随后，本项目组参加了国际2型糖尿病1q协作组，在该区段通过高密度SNP关联分析，以及6482例大样本中国人群的关联研究，发现NOS1AP基因变异与中国人2型糖尿病易感性密切相关。且NOS1AP基因变异与2型糖尿病者口服瑞格列奈降糖疗效以及心电参数——QT间期相关。我们对NOS1AP-rs12742393变异进行表达谱和蛋白质谱研究，发现携带不同基因型个体的肝脏表达谱和血清蛋白质谱存在差异。我们还通过大样本关联研究，验证了9个基因变异与中国人2型糖尿病易感性相关。相关研究成果不仅有助于更好的理解2型糖尿病分子病因学发病机制，且有望为易感人群筛查及早期防治创造条件。
英文摘要
In our previous study, we had launched genome-wide scan for diabetes and identified a significant linkage signal on chromosome 1q. This result was also replicated in several independent related studies. We then joined the International Type 2 Diabetes 1q Consortium to initiate high-density SNP-based association study. Analysis of data from more than 4000 SNP on chromosome 1q for over 4000 samples has already identified several regions associated with diabetes. We then follow-up the 1q signals and found that NOS1AP variations were associated with type 2 diabetes susceptibility in the Chinese population (N=6,482). We also found that genetic variants of NOS1AP were associated with repaglinide efficacy and QT interval duration in Chinese type 2 diabetic patients. We found the gene expression profiles of human liver tissue and serum proteome profiles were significant different among risk allele carriers and non-carriers of NOS1AP-rs12742393. In addition, we also identified that nine gene variations were associated with type 2 diabetes susceptibility in the Chinese population. Such work will not only enhance our understanding of molecular pathology in type 2 diabetes, but also provide information in finding related biomarkers to the susceptibility of type 2 diabetes.
结题摘要
本项目组在全基因组扫查中，经家系连锁分析将中国人2型糖尿病易感基因定位在1q区域，同时国际上多个独立研究也将2型糖尿病易感基因定位在该区段。随后，本项目组参加了国际2型糖尿病1q协作组，在该区段通过高密度SNP关联分析，以及6482例大样本中国人群的关联研究，发现NOS1AP基因变异与中国人2型糖尿病易感性密切相关。且NOS1AP基因变异与2型糖尿病者口服瑞格列奈降糖疗效以及心电参数——QT间期相关。我们对NOS1AP-rs12742393变异进行表达谱和蛋白质谱研究，发现携带不同基因型个体的肝脏表达谱和血清蛋白质谱存在差异。我们还通过大样本关联研究，验证了9个基因变异与中国人2型糖尿病易感性相关。相关研究成果不仅有助于更好的理解2型糖尿病分子病因学发病机制，且有望为易感人群筛查及早期防治创造条件。