药代动力学相关基因多态与中国汉族人群寿命相关性研究

发布时间：2018-08-30 18:50

【摘要】：目的：一些处置药物的蛋白在人群中存在导致活性缺失的多态变异。这些变异显著影响药物临床治疗,也改变机体对许多内源活性物质以及环境毒物的应激处置能力。药物处置相关蛋白基因多态与一些死亡率居前的心血管病、肿瘤等疾病显著相关。人的寿命是遗传与环境共同决定的复杂表型。疾病与机体应激能力是影响寿命重要因素。该课题研究具有重要生理与病理学意义的药物处置相关蛋白基因多态与寿命表型的相关性。 方法：对328名85岁以上(包括85岁)健康老年人和314名性别、居住环境等相匹配的健康志愿者(年龄小于60岁)采用PCR-RFLP检测基因组DNA CYP2C9*3, CYP3A5*3, CYP2C19*2,*3及SLCO181T521C单核苷酸多态性。收集研究对象的一般资料,包括姓名、性别、年龄、身高/体重等。同时按照性别进行分层分析,统计分析各基因多态性在高龄组与对照组之间有无显著性差异。 结果：CYP2C9*3, CYP3A5*3,CYP2C19*2,*3以及SLCO1B1T521C的基因型在高龄组和对照组中均符合Hardy-Weinberg平衡。五个基因位点在高龄组和对照组中的分布频率无显著差异。当用三种遗传模型分别对五个基因位点在高龄组和对照组的分布结果进行分析发现,五个基因位点在高龄组和对照组中的分布也基本齐同。将高龄组人群按照性别进行分层分析,未发现显著性差异存在。当将高龄组年龄限制为≥95岁时,各基因型在高龄组和对照组中的分布也基本一致。 结论：本课题首次探讨了药代动力学相关基因多态与中国汉族人群寿命之间的相关性,发现CYP2C9*3、CYP2C19*2、CYP2C19*3、 CYP3A5*3、SLCO181T521C基因多态对中国汉族人群的寿命没有显著影响。
[Abstract]:Objective: some drug-disposing proteins have polymorphic variations that lead to loss of activity in the population. These variations significantly affect the clinical treatment of drugs, but also change the ability of the body to deal with many endogenous active substances and environmental poisons. The polymorphism of drug disposal associated protein gene is significantly associated with some diseases such as cardiovascular disease, tumor and so on. Life expectancy is a complex phenotype determined by heredity and environment. Disease and stress ability are important factors affecting life span. In this study, we studied the relationship between polymorphism of drug disposal associated protein gene and lifetime phenotype, which has important physiological and pathological significance. Methods: PCR-RFLP was used to detect genomic DNA CYP2C9*3, CYP3A5*3, CYP2C19*2,*3 and SLCO181T521C single nucleotide polymorphisms in 328 healthy volunteers aged over 85 years (including 85 years old) and 314 healthy volunteers (aged less than 60 years) who matched their sex and living environment. Collect general information about the subjects, including name, sex, age, height / weight, etc. At the same time, stratified analysis according to sex, statistical analysis of the polymorphism of each gene between the elderly group and the control group there was significant difference. Results the genotypes of CYP2C9, CYP3A5*3,CYP2C19*2,*3 and SLCO1B1T521C in the aged group and the control group all accord with the Hardy-Weinberg balance. There was no significant difference in the distribution of the five loci between the aged group and the control group. The distribution of five gene loci in the aged group and the control group were analyzed with three genetic models, and the distribution of the five loci in the aged group and the control group was basically the same. There was no significant difference in the age group by sex stratification analysis. When the age of the elderly group was limited to 鈮，

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