脂肪细胞因子家族基因多态性与动脉粥样硬化性脑梗死的相关性研究

The dys-regulation of adipokine secretion is a major contributor to atherosclerosis and numerous metabolic and inflammatory diseases. So far It is not entirely clear that the biological effect of adipokine gene variants to the atherosclerotic cerebral infarction (ACI), Now this project intends to: 1)using genetic association study method based on DNA pooling screened single nucleotide polymorphisms (SNPs) of adipokine closely linked to ACI; 2)adopting the strategy called Transmission-Disequilibrium Test(TDT) to screen out the SNPs of adipokine closely associated with ACI in numerous nuclear families data of ACI, confirme the genotype and related SNPs and haplotype closely linked with ACI patients in Changsha population; 3)establish a database that including the relevant information about ACI patients and their family members and the related risk factors associated with ACI, using the advanced statistical methods, such as proportional hazards, conditional logistic regression model and so on, definitize the risk factors closely linked with the SNPs and haplotype of adopokine that associated with ACI; 4)investigating the function and bioactivity of SNPs and haplotype, explore the influence of ACI in consequence of.some changes of protein conformation and molecular signaling pathways. Illuminate the pathogenic mechanism of ACI in consequence of adipokine variation from molecular level, It will be of great significance to checkout in early stage and take prevention measures towards susceptible patients of ACI.

脂肪细胞因子紊乱可导致动脉粥样硬化及其相关疾病。目前尚不完全清楚脂肪细胞因子基因变异对动脉粥样硬化性脑梗死（ACI）的影响，本研究拟：1）用基于DNA pooling的基因关联性研究方法筛选出脂肪因子与ACI相关的单核苷酸多态性（SNPs）；2）采用传递不平衡检验（TDT）策略在大量ACI 核心家系中筛查与ACI相关的脂肪因子基因的SNPs位点，确认长沙人群ACI相关基因及其相关SNPs和单体型。3）建立ACI 家系成员及患者的相关资料和ACI相关危险因子的数据库，运用proportional-hazards、条件logistic 回归模型等高级统计方法，明确与ACI 相关的脂肪细胞因子SNPs及单体型和密切相关的危险因素。4）研究SNPs及单体型功能，探讨蛋白构象及通路变化对ACI的影响。从分子水平阐明脂肪细胞因子对ACI的致病机制，对ACI易感患者早期检出和预防具有重要意义。