早发性冠心病生物标志物筛选和鉴定的研究

The environmental and genetic factors contribute to the risk of early-onset coronary heart disease (EOCAD). With the social and economic development, the incidence and mortality of EOCAD around the developing countries continue to rise. Therefore, screening and identification clinical laboratory biomarkers of EOCAD are important for prevention and control of the disease.. Plasma proteins play many important roles，including transport of lipids, hormones, vitamins and minerals in the circulatory system，the regulation of acellular activity and functioning of the immune system,and maintaining homeostasis in the internal environment. With the occurrence of diseases, the levels of plasma proteins and gene-expression will be changed. Complex disease is influenced by multiple genetic and environmental factors. As a complex disease, the occurrence of EOCAD may associate with many gene mutations.. In this study, we use iTRAQ and protein array techniques to screen differentially expressed proteins in plasma, PCR array was used to screen the differentially expressed genes in blood, mutation analysis of candidate genes was used to screen susceptibility genes. Then, these biomarkers of EOCAD were also be tested and identified. The results offer useful references for further study on the mechanism of EOCAD, and determination of the EOCAD risk.

早发性冠心病的发生与环境和遗传因素有密切关系。随着社会经济的发展，特别是在发展中国家早发性冠心病的发病率和死亡率均不断升高。因此筛选和鉴定早发性冠心病发病风险的生物标志物对疾病的预防和控制有一定意义。. 血浆蛋白发挥许多重要作用，如运输脂质，激素，维生素和矿物质，调节细胞活性和免疫功能，维持机体内环境的稳态。疾病发生过程中部分血浆蛋白质水平也会发生变化。此外，血液中的基因表达水平也会发生改变。复杂疾病受到多基因与环境因素的共同影响，作为一种复杂疾病，早发性冠心病的发生可能与多个基因的遗传变异相关。. 课题拟利用iTRAQ技术，蛋白芯片技术筛选早发性冠心病血浆差异蛋白。应用PCR芯片技术筛选差异表达的基因。候选基因突变分析的方法筛选易感基因。并对筛选出的早发性冠心病生物标志物进行验证和鉴定。研究结果可为进一步研究早发性冠心病的发生机制，判定早发性冠心病的风险提供依据。

近年来，罹患冠心病的人年龄有下降的趋势，且早发性冠心病的患病率逐年增加，因此筛选和鉴定疾病相关生物标志物对疾病的预防控制有一定意义。.本研究主要围绕以下几个问题展开：（1）利用蛋白质组学方法筛选新的早发性心肌梗死血清标志物。（2）血清ADMA水平与早发性冠心病危险性的关系。（3）探讨血清尿酸（UA）与早发性冠心病的关系。（4）血清腺苷脱氨酶（ADA）活性与冠心病的关系。（5）探讨中国人群MTHFR基因常见变异与早发性冠心病的关系。（6） 探讨中国人群Alstrom综合征（ALMS 1）基因与早发性冠心病的关系。.总之，我们筛选了妊娠区蛋白（PZP）和亮氨酸富集ɑ-2-糖蛋白（LRG）作为早发性心肌梗死的血清生物标志物并进行了验证和鉴定。明确了非对称二甲基精氨酸、尿酸、腺苷脱氨酶、同型半胱氨酸与早发性冠心病的关系。探索了MTHFR基因和ALMS1基因与早发性冠心病风险的关系。研究结果对早发性冠心病病理生理研究和疾病的预防、控制、治疗等有一定价值。