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

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

doi:10.1186/s12920-020-00857-z

Abstract

BackgroundInternalizing 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).ResultsWe 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.ConclusionsTERT 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.

Highlights

Internalizing mental disorders (IMDs) have been associated with accelerated telomere length (TL) attrition; this association has not been investigated in the context of genetic variation that has been found to influence TL
Using the same samples of Ugandan HIV+ children and adolescents, we previously found that TL was longer at baseline in cases with IMDs, but that this difference did not remain 12 months later [10]
We found that telomerase reverse transcriptase gene (TERT) rs2736100 and telomerase RNA component gene (TERC) rs16847897 significantly moderated the association between IMDs and TL at 12 months

Summary

Introduction

Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; this association has not been investigated in the context of genetic variation that has been found to influence TL. Kalungi et al BMC Med Genomics (2021) 14:15 Studies undertaken both in the developed (Europe and the United States) and developing world (sub-Saharan Africa) among HIV+ children and adolescents have documented rates of major depressive disorder of between 12.7 and 40% [2,3,4,5,6,7,8], and rates of anxiety disorders of between 9 and 32.2% [1,2,3, 6]. The etiology of IMDs, and the biochemical and molecular contributions in particular, are largely unknown

Methods

Results

Discussion

Conclusion