外周血白细胞端粒长度与轻度认知障碍老年人发生风险关联的病例对照研究

杨桐; 王华楼; 陈冲; 赵会朝; 熊英; 贾晶雅; 张美琳; 马菲

doi:10.16462/j.cnki.zhjbkz.2020.04.008

外周血白细胞端粒长度与轻度认知障碍老年人发生风险关联的病例对照研究

doi: 10.16462/j.cnki.zhjbkz.2020.04.008

杨桐^{1, 2},
王华楼^{1, 2},
陈冲³,
赵会朝⁴,
熊英⁵,
贾晶雅^{1, 2},
张美琳^{2, 6},
马菲^{1, 2, ,}

1.
300070 天津, 天津医科大学公共卫生学院流行病与卫生统计学系
2.
300070 天津, 天津市环境营养与人群健康重点实验室
3.
300060 天津, 天津医科大学肿瘤医院检验科
4.
300070 天津, 天津医科大学医学人文学院
5.
300191 天津, 天津市南开区王顶堤医院社区科
6.
300070 天津, 天津医科大学公共卫生学院营养与食品卫生学系

基金项目: 国家自然科学基金面上项目(81874261, 81573148)

详细信息

通讯作者:
马菲, E-mail:mafei@tmu.edu.cn

中图分类号: R749.1
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- 文章访问数: 406
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- 被引次数: 0
出版历程
- 收稿日期: 2019-10-19
- 修回日期: 2020-01-09
- 刊出日期: 2020-04-10

Association of leukocyte telomere length in peripheral blood and the risk of mild cognitive impairment in elderly subjects:a case-control study

YANG Tong^{1, 2},
WANG Hua-lou^{1, 2},
CHEN Chong³,
ZHAO Hui-chao⁴,
XIONG Ying⁵,
JIA Jing-ya^{1, 2},
ZHANG Mei-lin^{2, 6},
MA Fei^{1, 2
, ,}

1.
Department of Epidemiology and Health Statistics, Faculty of Public Health, Tianjin Medical University, Tianjin 300070, China
2.
Tianjin Key Laboratory of Environmental Nutrition and Population Health, Tianjin 300070, China
3.
Department of Clinical Laboratory, Cancer Hospital, Tianjin Medical University, Tianjin 300060, China
4.
Faculty of Medicine and Humanities, Tianjin Medical University, Tianjin 300070, China
5.
Community Department, Wangdingdi Hospital, Nankai District, Tianjin 300191, China
6.
Department of Nutrition and Food Hygiene, Faculty of Public Health, Tianjin Medical University, Tianjin 300070, China

Funds: National Natural Science Foundation of China(81874261, 81573148)

More Information

Corresponding author: MA Fei, E-mail:mafei@tmu.edu.cn

摘要

摘要: 目的探讨轻度认知障碍(mild cognitive impairment, MCI)老年人外周血白细胞端粒长度(leukocyte telomere length, LTL)与MCI发生风险之间的关联。方法于2017年10月-2017年12月在天津市南开区王顶堤街道的5个社区纳入MCI和健康对照老年受试者进行病例对照设计, 实施问卷调查和静脉血样采集, 用实时荧光定量多聚核苷酸链式反应(real-time quantitative polymerase chain reaction, qPCR)进行LTL的测量。采用多元Logistic回归分析模型分析LTL不同水平与MCI发生风险之间的关联。结果两组受试对象都为183例。MCI组LTL水平(1.44±0.23)低于对照组(1.66±0.23), 两组差异具有统计学意义(Z=-8.94, P < 0.001)。调整年龄、性别、教育程度、吸烟、饮酒、糖尿病、高血压、心脏病后, 较低水平LTL与MCI发生风险存在统计学意义关联(均有P < 0.05);与LTL第一水平组相比, 其二、三、四水平组MCI发生风险的比值比(odds ratio, OR)及95%置信区间(95% confidence interval, 95% CI)分别为0.262(0.130~0.531)、0.088(0.043~0.180)、0.083(0.040~0.169)。结论外周血白细胞短端粒可能是MCI发生的独立危险因素, 并且随着LTL缩短, MCI发生风险增加。
- 轻度认知障碍 /
- 端粒 /
- 病例对照研究 /
- 多元Logistic回归分析模型
Abstract: Objective To explore the relationship between leukocyte telomere length(LTL)in peripheral blood and the risk of mild cognitive impairment(MCI)in elderly subjects. Methods This was a case-control study. Healthy controls and subjects with MCI were recruited from five communities in Wangdingdi Street, Nankai District, Tianjin from October 2017 to December 2017. Questionnaires were conducted and venous blood samples were collected from each subject. LTL was assessed using real-time quantitative polymerase chain reaction assay(qPCR). Multiple logistic regression model was performed to analyze the relationship between LTL for each level group and the risk of MCI. Results A total of 183 participants was enrolled for each group. The level of serum LTL was 1.44±0.23 in the MCI group, which was lower than 1.66±0.23 in the control group(Z=-8.94, P < 0.001). There was a significant correlation between lower levels of LTL and the risk for MCI after adjusting variables for age, gender, education, smoking, alcohol consumption, diabetes, hypertension, and heart disease(allP < 0.05). Compared with the first level group of LTL, the adjusted odds ratio(OR) and 95% confidence interval(95% CI) for the risk of MCI were 0.262(0.130-0.531) for the second level group, 0.088(0.043-0.180) for the third level group, and 0.083(0.040-0.169) for the fourth level group. Conclusions Short leukocyte telomere length in peripheral blood appears to be an independent risk factor for the incidence of MCI. And with the decrease of LTL, the risk of MCI increased.
- Mild cognitive impairment /
- Telomere /
- Case-control study /
- Multiple logistic regression

HTML全文

图 1 端粒长度与MCI发生风险OR值及95% CI的森林图

注:图中OR值及95% CI是LTL的各水平组相比第一水平组LTL≤1.381得来的。其中(●)代表未调整的模型; (▲)代表调整年龄、性别、文化程度后的模型; (■)代表调整年龄、性别、文化程度、吸烟、饮酒、心脏病、糖尿病、高血压后的模型。

Figure 1. Forest plots of telomere length and MCI showing OR and 95% CI

下载: 全尺寸图片幻灯片

表 1 研究人群的人口统计学和临床特征[n(%)]

Table 1. Demographic and clinical characteristics of the study population[n(%)]

变量	MCI组(n=183)	对照组(n=183)	t/Z/χ²值	P值
人口学变量
年龄(岁)	66.91±5.67	68.07±5.89	-2.07	0.039
男性	82(44.81)	64(34.97)	3.69	0.055
教育程度(年)	9.60±2.69	9.60±2.69	0.00	1.000
生活方式
BMI(kg/m²)	25.16±3.20	24.19±3.14	3.25	0.001
吸烟	13(7.10)	11(6.01)	0.18	0.673
饮酒	17(9.29)	16(8.74)	0.03	0.855
既往史
糖尿病	27(14.75)	26(14.21)	0.02	0.882
高血压	67(36.61)	71(38.80)	0.19	0.666
心脏病	11(6.01)	12(6.56)	0.05	0.830
生化指标
LTL^a	1.44±0.23	1.66±0.23	-8.94	< 0.001
MMSE^b	22.58±1.96	25.58±1.96	-12.63	< 0.001
注:^aLTL表示为T/S比率-端粒DNA(T)与单拷贝基因(S)的拷贝数; ^bMMSE表示量表评分分值。

下载: 导出CSV

表 2 端粒长度与MCI发生风险关联的多元Logistic回归分析模型

Table 2. Multiple Logistic regression model analysis of relationship between telomere length and risk of MCI

端粒长度四分位数组别	例数		模型1^a		模型2^b		模型3^c
端粒长度四分位数组别	MCI组	对照组	OR(95% CI)值	P值	OR(95% CI)值	P值	OR(95% CI)值	P值
LTL≤1.381	76	16	1.000		1.000		1.000
1.381 < LTL≤1.535	53	38	0.294(0.149~0.580)	0.123	0.270(0.135~0.541)	0.215	0.262(0.130~0.531)	0.025
1.535 < LTL≤1.695	28	64	0.092(0.046~0.185)	< 0.001	0.090(0.044~0.182)	< 0.001	0.088(0.043~0.180)	< 0.001
LTL > 1.695	26	65	0.084(0.042~0.171)	< 0.001	0.083(0.041~0.170)	< 0.001	0.083(0.040~0.169)	< 0.001
注:^a模型1未进行调整; ^b模型2调整年龄、性别、教育程度; ^c模型3调整年龄、性别、教育程度、吸烟、饮酒、糖尿病、高血压、心脏病。

下载: 导出CSV

参考文献(18)

[1]	Alzheimer's Association. 2016 Alzheimer's disease facts and figures[J]. Alzheimers Dement, 2016, 12(4): 459-509. DOI: 10.1016/j.jalz.2016.03.001.
[2]	Wimo A. The end of the beginning of the Alzheimer's disease nightmare: a devil's advocate's view[J]. J Alzheimers Dis, 2018, 64(s1): S41-S46. DOI: 10.3233/JAD-179905.
[3]	Mancioppi G, Fiorini L, Timpano SM, et al. Novel technological solutions for assessment, treatment, and assistance in mild cognitive impairment[J]. Front Neuroinform, 2019, 13(58): 1-23. DOI: 10.3389/fninf.2019.00058.
[4]	Tedone E, Arosio B, Colombo F, et al. Leukocyte telomere length in Alzheimer's disease patients with a different rate of progression[J]. J Alzheimers Dis, 2015, 46(3): 761-769. DOI: 10.3233/JAD-142808.
[5]	Zhan YQ, Song C, Robert K, et al. Telomere length shortening and Alzheimer disease-a mendelian randomization study[J]. JAMA Neuro, 2015, 72(10): 1202-1203. DOI: 10.1001/jamaneurol.2015.1513.
[6]	Ma F, Lv X, Du Y, et al. Association of leukocyte telomere length with mild cognitive impairment and Alzheimer's disease: role of folate and homocysteine[J]. Dement Geriatr Cogn Disord, 2019, 1-12. DOI: 10.1159/000501958.
[7]	Scarabino D, Broggio E, Gambina G, et al. Leukocyte telomere length in mild cognitive impairment and Alzheimer's disease patients[J]. Exp Gerontol, 2017, 98: 143-147. DOI: 10.1016/j.exger.2017.08.025.
[8]	Lau H, Mat AF, Rajab NF, et al. Identification of neuroprotective factors associated with successful ageing and risk of cognitive impairment among Malaysia older adults[J]. Curr Gerontol Geriatr Res, 2017, 2017(7): 1-7. DOI: 10.1155/2017/4218756.
[9]	Roberts RO, Boardman LA, Cha RH, et al. Short and long telomeres increase risk of amnestic mild cognitive impairment[J]. Mech Ageing Dev, 2014, 1(141-142): 64-69. DOI: 10.1016/j.mad.2014.10.002.
[10]	Leigh H. Diagnostic and statistical manual of mental disorders(DSM)[M]. Encyclopedia of clinical neuropsychology cham; Springer International Publishing, 2018: 1-4. DOI: 10.1007/978-3-319-56782-2_9129-1.
[11]	韩睿婕.病例对照分析法样本容量及基因外显率参数的估计方法[D].杨凌: 西北农林科技大学, 2009. Han RJ. Estimating sample size and penetrance parameters for case-control design of candidate-gene associations[D]. Yangling: Northwest A & F University, 2009.
[12]	Cawthon RM. Telomere measurement by quantitative PCR[J]. Nucleic acids research, 2002, 30(10): e47. DOI: 10.1093/nar/30.10.e47.
[13]	Innes KE, Selfe TK, Brundage K, et al. Effects of meditation and music-listening on blood biomarkers of cellular aging and Alzheimer's disease in adults with subjective cognitive decline: an exploratory randomized clinical trial[J]. J Alzheimers Dis, 2018, 66(3): 947-970. DOI: 10.3233/JAD-180164.
[14]	Sindi S, Ngandu T, Hovatta I, et al. Baseline telomere length and effects of a multidomain lifestyle intervention on cognition: the FINGER randomized controlled trial[J]. J Alzheimers Dis, 2017, 59(4): 1459-1470. DOI: 10.3233/JAD-170123.
[15]	Tonnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer's disease[J]. J Alzheimers Dis, 2017, 57(4): 1105-1121. DOI: 10.3233/JAD-161088.
[16]	Mota SI, Costa RO, Ferreira IL, et al. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease[J]. Biochim Biophys Acta, 2015, 1852(7): 1428-1441. DOI: 10.1016/j.bbadis.2015.03.015.
[17]	Ahmed W, Lingner J. Impact of oxidative stress on telomere biology[J]. Differentiation, 2018, 99(21-27). DOI: 10.1016/j.diff.2017.12.002.
[18]	Cai Z, Yan LJ, Ratka A. Telomere shortening and Alzheimer's disease[J]. Neuromolecular Med, 2013, 15(1): 25-48. DOI: 10.1007/s12017-012-8207-9.