【摘要】：目的：一些處置藥物的蛋白在人群中存在導(dǎo)致活性缺失的多態(tài)變異。這些變異顯著影響藥物臨床治療,也改變機(jī)體對(duì)許多內(nèi)源活性物質(zhì)以及環(huán)境毒物的應(yīng)激處置能力。藥物處置相關(guān)蛋白基因多態(tài)與一些死亡率居前的心血管病、腫瘤等疾病顯著相關(guān)。人的壽命是遺傳與環(huán)境共同決定的復(fù)雜表型。疾病與機(jī)體應(yīng)激能力是影響壽命重要因素。該課題研究具有重要生理與病理學(xué)意義的藥物處置相關(guān)蛋白基因多態(tài)與壽命表型的相關(guān)性。 方法：對(duì)328名85歲以上(包括85歲)健康老年人和314名性別、居住環(huán)境等相匹配的健康志愿者(年齡小于60歲)采用PCR-RFLP檢測(cè)基因組DNA CYP2C9*3, CYP3A5*3, CYP2C19*2,*3及SLCO181T521C單核苷酸多態(tài)性。收集研究對(duì)象的一般資料,包括姓名、性別、年齡、身高/體重等。同時(shí)按照性別進(jìn)行分層分析,統(tǒng)計(jì)分析各基因多態(tài)性在高齡組與對(duì)照組之間有無(wú)顯著性差異。 結(jié)果：CYP2C9*3, CYP3A5*3,CYP2C19*2,*3以及SLCO1B1T521C的基因型在高齡組和對(duì)照組中均符合Hardy-Weinberg平衡。五個(gè)基因位點(diǎn)在高齡組和對(duì)照組中的分布頻率無(wú)顯著差異。當(dāng)用三種遺傳模型分別對(duì)五個(gè)基因位點(diǎn)在高齡組和對(duì)照組的分布結(jié)果進(jìn)行分析發(fā)現(xiàn),五個(gè)基因位點(diǎn)在高齡組和對(duì)照組中的分布也基本齊同。將高齡組人群按照性別進(jìn)行分層分析,未發(fā)現(xiàn)顯著性差異存在。當(dāng)將高齡組年齡限制為≥95歲時(shí),各基因型在高齡組和對(duì)照組中的分布也基本一致。 結(jié)論：本課題首次探討了藥代動(dòng)力學(xué)相關(guān)基因多態(tài)與中國(guó)漢族人群壽命之間的相關(guān)性,發(fā)現(xiàn)CYP2C9*3、CYP2C19*2、CYP2C19*3、 CYP3A5*3、SLCO181T521C基因多態(tài)對(duì)中國(guó)漢族人群的壽命沒(méi)有顯著影響。
[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，

本文編號(hào)：2213981