GH-IGF1通路基因多态性与AGHD患者认知功能改善个体化差异的关联研究

Cognitive function impairment is a determinant factor of life quality and long term prognosis of adult growth hormone deficiency. Recombinant human growth hormone replacement can significantly improve cognitive function but inter-individual variations exist among patients. GH-IGF1pahtway gene polymorphisms have been reported to related to inter-individial responses of GHD in children. Our working hypothesis is that GH-IGF1 pathway gene polymorphisms are also related to cognitive function improvement levels in AGHD patients. In recent 30 years, we have set up a database including more than 300 cases of childhood onset AGHD. In this project, we are going to investigate the effect of rhGH on cognitive function improvement in AGHD patients and the relationship between GH-IGF1 pathway gene polymorphism (including GHR fl/d3, PIK3CB re361072、JAK2 rs7849191、JAK2 rs3780378 and STAT5B rs6503691). All these multi-diciplinary research will lead to novel understanding of cognitive function pathogenesis and inter-individual variation of rhGH replacement in AGHD patients.

生长激素(GH)是影响认知功能的重要因素。成人生长激素缺乏症(AGHD)患者认知功能显著下降，重组人生长激素(rhGH)替代治疗能有效改善认知功能，但疗效存在个体差异。文献报道GH-IGF1通路基因多态性与rhGH改善儿童GHD患者身高和代谢指标的个体差异相关，因此我们推测该通路基因多态性也是影响AGHD患者认知功能改善个体差异的重要因素。本项目拟在已有大宗AGHD临床数据库的基础上，联合应用神经心理学检测和脑功能核磁成像，评价rhGH改善AGHD患者认知功能的个体差异，研究GH-IGF1通路关键因子基因多态性位点(包括GHR fl/d3多态性、PIK3CB re361072、JAK2 rs7849191和rs3780378、STAT5B rs6503691)与上述个体差异之间的关联，寻找AGHD患者认知功能改善个体化差异的预测指标，为AGHD患者个体化替代治疗提供新的实验数据。

生长激素是影响认知功能的重要因素。成人生长激素缺乏症（adult growth hormone deficiency，AGHD）患者认知功能显著下降，重组人生长激素（rhGH）替代治疗能有效改善认知功能，但存在个体差异。本项目拟在大宗AGHD临床数据库的基础上，联合应用神经心理学检测和脑功能核磁成像，评价rhGH改善AGHD患者认知功能的个体差异，研究GH-IGF1通路关键因子基因多态性位点与上述个体差异之间的关联。在本项目的实施过程中，我们建立了目前全球单中心数量最大的COAGHD临床数据，作为牵头单位在全国开展多中心rhGH治疗AGHD的临床研究，建立了中国成人IGF1的正常参考范围；率先在中国COAGHD人群中开展了神经认知评价以及功能核磁成像研究；完成了GH-IGF1基因通路多态性的检测。通过上述研究，目前发表SCI论文3篇，国内核心期刊论文1篇。