广西长寿地区人群白细胞DNA总体甲基化水平探究.docVIP

广西长寿地区人群白细胞DNA总体甲基化水平探究 　 作者：张志勇 李春宏 仇小强 农清清 何敏 覃健 蒋贵发 黄明立 【摘要】 目的 比较广西长寿地区巴马县人群与一般地区人群的白细胞DNA总体甲基化水平，探讨长寿与DNA甲基化之间可能存在的关系。方法 (1)在巴马县长寿村落抽取健康个体199人组成实验组，另抽取与实验组年龄性别相匹配的个体163人组成对照组。(2)取研究对象外周血2 ml，分离白细胞、提取DNA，用高效液相色谱法检测其中胞嘧啶(dC)和5甲基胞嘧啶(5dmC)浓度，计算5dmC/(dC+5dmC)比值，以比值代表研究对象总体甲基化水平。结果 (1)对照组和实验组研究对象的总体甲基化水平都呈增龄性下降，下降速率分别为-0.874 3和-1.151 7，年龄与甲基化比值呈负相关，相关系数分别是-0.480和-0.639；(2)实验组人群DNA总体甲基化水平比对照组的高(P＜0.001)；分年龄组段比较，在10～、20～、40～、50～、60～年龄段，实验组人群的甲基化水平高于对照组(P＜0.05)。 结论 巴马县人群长寿与其DNA总体甲基化水平较高可能有一定的关系。 【关键词】 巴马县；长寿；DNA总体甲基化水平 【Abstract】Objective To compare the total methylation level of the leukocytes from persons living in the longevity district Bama county of Guangxi province with from general district, and study possible relationship between the longevity and DNA methylation. Methods 199 healthy individuals in the longevity villages of Bama were selected as case group and another 163 healthy individuals as control group living in general district. 2 ml vein blood was obtained from the subjects to extract DNA and then detect the concentrations of the dC and 5dmC with the HPLC and calculate the value of 5dmC/(dC+5dmC) which represents the subjects total methylation level. Results The total methylation level declined with aging in control and case groups by -0.874 3 and -1.151 7 respectively. Age was negatively correlated to 5dmC/(dC+5dmC) value (r=-0.506 2 and -0.666 6 respectively). The total methylation level of the case group was higher than that of control group(P＜0.001). Analyzing in details, in the year of 10～, 20～, 40～, 50～ and 60～，5dmC/(dC+5dmC) value in case group was higher than that of control group. Conclusions There is relationship between individuals longevity in Bama county and their higher total DNA methylation level. 【Key words】Bama County; Longevity; DNA total methylation level 　　衰老是由一系列基因激活和阻抑及其通过各自表达产物相互作用的结果。DNA甲基化是有核细胞特有的复制后修饰，与肿瘤、遗传病、自身免疫性疾病、衰老的发生密切相关〔1〕。研究表明多数动物的组织或器官基因组中5甲基胞嘧啶(5dmC) 含量随年龄增加而下降〔2〕，Wilson等〔3〕发现培养的人二倍体成纤维细胞中5dmC含量随培养代数增加