TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda

Kalungi, Allan; Kinyanda, Eugene; Womersley, Jacqueline S.; Joloba, Moses; Ssembajjwe, Wilber; Nsubuga, Rebecca N.; Kaleebu, Pontiano; Levin, Jonathan; Kidd, Martin; Seedat, Soraya; Hemmings, Sian

doi:10.1186/s12920-020-00857-z

Cited by 5 publications

(2 citation statements)

References 89 publications

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“…Despite the published findings on the relation of shortening of telomeres to the presence of a minor allele of TERC rs1317082 and their increase with a minor allele of OBFC1 rs2487999 [ 7 ], we failed to detect such associations. Despite the declared hypothesis on the association between telomere length and depression level and published data on the effect of TERT and TERC SNPs in manifestation of internalizing problems (depression, anxiety, and post-traumatic stress disorder) [ 3 , 24 ], we did not confirm these associations between genetic variants and depression level in mentally healthy young adults.…”

Section: Discussioncontrasting

confidence: 99%

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

Казанцева

Davydova²,

Enikeeva³

et al. 2022

Russ J Genet

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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 ( TERT rs7726159), telomerase RNA component ( TERC rs1317082), and the CST complex encoding protein ( OBFC1 rs2487999) gene polymorphisms was performed with RTL and depression level in mentally healthy individuals ( N = 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 ( P = 4.3е–4; r 2 = 0.018), which included rs7726159 in the TERT gene ( P = 0.020; β = 0.078) and such environmental predictors as age ( P = 0.001; β = –0.027) and place of residence in childhood (urban/rural area) ( P = 0.048; β = 0.063). The data obtained confirm the involvement of TERT 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.

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Section: Discussioncontrasting

confidence: 99%

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

Казанцева

Davydova²,

Enikeeva³

et al. 2022

Russ J Genet

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“…The procedure for selection of cases and controls has been previously described (Kalungi et al, 2021). Briefly, all cases were stratified by site, sex, age category, and SES, resulting in a total of 36 strata.…”

Section: Selection Of Cases and Controlsmentioning

confidence: 99%

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda

et al. 2021

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Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs.Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs.Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.

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MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

Zhang

Yang

et al. 2021

Cell Biology International

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Alzheimer′s disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d‐galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aβ42 oligomers. POT1 expression in the AD model was detected by quantitative real‐time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual‐luciferase assay was used to validate the targeted binding relationship between microRNA‐340‐5p (miR‐340‐5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aβ1–42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual‐luciferase assay verified the binding relationship between miR‐340‐5p and POT1. An increase in miR‐340‐5p expression could alleviate cellular senescence and AD symptoms. miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.

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TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda

Cited by 5 publications

References 89 publications

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

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

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda

MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

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