Allan Kalungi1,2,3,4, Eugene Kinyanda5,6, Jacqueline S Womersley7,8, Moses L Joloba9,10, Wilber Ssembajjwe5,11, Rebecca N Nsubuga11, Pontiano Kaleebu12, Jonathan Levin13, Martin Kidd14, Soraya Seedat7,8, Sian M J Hemmings7,8. 1. Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. allankalungi1@gmail.com. 2. Mental Health Section, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda. allankalungi1@gmail.com. 3. Department of Medical Microbiology, Makerere University, Kampala, Uganda. allankalungi1@gmail.com. 4. Department of Psychiatry, College of Health Sciences, Makerere University, Kampala, Uganda. allankalungi1@gmail.com. 5. Mental Health Section, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda. 6. Department of Psychiatry, College of Health Sciences, Makerere University, Kampala, Uganda. 7. Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. 8. South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 9. Department of Medical Microbiology, Makerere University, Kampala, Uganda. 10. School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda. 11. Statistics and Data Science Section, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda. 12. MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda. 13. School of Public Health, University of Witwatersrand, Johannesburg, South Africa. 14. Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Cape Town, South Africa.
Abstract
BACKGROUND: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years). RESULTS: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. CONCLUSIONS: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.
BACKGROUND: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years). RESULTS: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. CONCLUSIONS: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.
Entities:
Keywords:
HIV+ children and adolescents; Internalizing mental disorders; TERC rs16847897; TERT rs2736100; Telomere length attrition; Uganda
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