Abstract
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Abstract; Background Internalizing mental disorders (IMDs) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation. A large genome-wide meta-analysis has implicated several loci that affect mean TL, in particular single nucleotide polymorphisms within the telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) genes. Genetic variations in the solute carrier family 6 member 4 gene (SLC6A4) and the tryptophan hydroxylase 2 (TPH2) genes have also been reported to moderate the association between social environment and TL. The SLC6A4 codes for the serotonin transporter (5-HTT), a protein that recycles serotonin from synapses while the TPH2 codes for tryptophan hydroxylase 2, an enzyme that catalyzes the rate-limiting reaction in serotonin biosynthesis. This case-control study used linear regression models to investigate the moderating effects of selected polymorphisms in TERT, TERC, SLC6A4 and TPH2 genes on the association between IMDs and relative TL (rTL), among Ugandan HIV+ children (7-11 years) and adolescents (12-17 years). Investigated polymorphisms were: rs2736100, rs7726159, rs10069690, and rs2853669 (TERT); rs12696304, rs16847897 and rs10936599 (TERC); 5-HTTLPR, rs35531, 5-HTTLPR/rs35531 and STin2.VNTRs (SLC6A4) and rs1843809, rs1386494, and rs34517220 (TPH2). Results At baseline, HIV+ children and adolescents with any internalizing mental disorder had significantly longer relative TL compared to controls matched for site, age, sex and socio-economic status (p = 0.001). None of the polymorphisms investigated had any moderating effect on the observed association between IMDs and baseline rTL. At 12 months, we observed no statistically significant difference in 12-month rTL between baseline cases and controls (p = 0.117), however, on modeling the effects of each of the selected polymorphisms, we observed that the interaction of IMDs and each of rs2736100 and rs16847897 significantly influenced rTL (p = 0.007 and p = 0.012 respectively). Conclusions The rs2736100 and rs16847897 polymorphisms moderate the association between IMDs and rTL among Ugandan HIV+ children and adolescents over time. The T-allele for rs2736100 and a C-allele for rs16847897 are associated with accelerated rTL attrition among cases of IMDs. The mechanisms under which these alleles interact with IMDs to moderate rTL require further investigations.