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心理健康受试者相对端粒长度的个体差异:基因多态性和城市居住情况的影响

Individual Differences in Relative Telomere Length in Mentally Healthy Subjects: The Effect of Gene Polymorphism and Urban Residency.

作者信息

Kazantseva A V, Davydova Yu D, Enikeeva R F, Mustafin R N, Lobaskova M M, Malykh S B, Khusnutdinova E K

机构信息

Institute of Biochemistry and Genetics-Subdivision of the Ufa Federal Research Centre, Russian Academy of Sciences, 450054 Ufa, Russia.

Bashkir State University, 450076 Ufa, Russia.

出版信息

Russ J Genet. 2022;58(9):1135-1144. doi: 10.1134/S1022795422090101. Epub 2022 Sep 13.

Abstract

The changes in the telomere length caused by the terminal underreplication in the existing literature are related to depressive disorders. However, the use of the telomere length as a biomarker of depressive states is ambiguous, which is due to the effect of various environmental factors on both the psychoemotional state and cellular aging of an organism. In order to identify the possible use of the relative telomere length (RTL) measured in peripheral blood leukocytes as a biomarker of enhanced liability to depression prior to the clinical symptoms, as well as to determine the link between telomere length, sociodemographic factors, allelic variants of the genes involved in the regulation of telomere elongation, and depression level, the association analysis of reverse transcriptase ( rs7726159), telomerase RNA component ( rs1317082), and the CST complex encoding protein ( rs2487999) gene polymorphisms was performed with RTL and depression level in mentally healthy individuals ( = 1065) aged 18-25 years. Together with genetic variants, the examined regression models included various sociodemographic parameters as predictors. As a result of statistical analysis, we failed to observe the association between RTL and individual differences in depression level in the studied sample. Nevertheless, multiple regression analysis allowed us to construct a statistically significant model of individual variance in RTL ( = 4.3е-4; = 0.018), which included rs7726159 in the gene ( = 0.020; β = 0.078) and such environmental predictors as age ( = 0.001; β = -0.027) and place of residence in childhood (urban/rural area) ( = 0.048; β = 0.063). The data obtained confirm the involvement of gene variants and age in telomere length in mentally healthy individuals aged 18-25 years and indicate a negative effect of urban residency on telomere length shortening, which reflects the cellular aging of an organism.

摘要

现有文献中因末端复制不足导致的端粒长度变化与抑郁症有关。然而,将端粒长度用作抑郁状态的生物标志物并不明确,这是由于各种环境因素对生物体的心理情绪状态和细胞衰老均有影响。为了确定在外周血白细胞中测量的相对端粒长度(RTL)作为临床症状出现前抑郁症易感性增强的生物标志物的可能用途,以及确定端粒长度、社会人口统计学因素、参与端粒延长调控的基因的等位基因变体与抑郁水平之间的联系,我们对18至25岁的心理健康个体(n = 1065)进行了逆转录酶(rs7726159)、端粒酶RNA组分(rs1317082)和编码CST复合体蛋白(rs2487999)基因多态性与RTL和抑郁水平的关联分析。除基因变异外,所检验的回归模型还纳入了各种社会人口统计学参数作为预测因子。统计分析结果显示,在研究样本中我们未观察到RTL与抑郁水平个体差异之间的关联。尽管如此,多元回归分析使我们能够构建一个RTL个体差异的统计学显著模型(R² = 4.3е-4;p = 0.018),该模型包括TERT基因中的rs7726159(p = 0.020;β = 0.078)以及年龄(p = 0.001;β = -0.027)和童年居住地(城市/农村地区)(p = 0.048;β = 0.063)等环境预测因子。所得数据证实了TERT基因变体和年龄参与18至25岁心理健康个体的端粒长度调节,并表明城市居住对端粒长度缩短有负面影响,这反映了生物体的细胞衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca94/9470233/083de2c656c3/11177_2022_1662_Fig1_HTML.jpg

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