Data Sheet 1_Naturally acquired malaria is associated with shorter leukocyte relative telomere length and increased hTERT expression in an endemic nigerian population.pdf

Background

Population-level studies have linked malaria endemicity to shorter leukocyte telomere length, but the patient-level molecular basis of this association remains unknown. This study investigated the associations of microscopy-confirmed malaria with relative leukocyte telomere length (rTL), human telomerase reverse transcriptase (hTERT) expression, parasite density, and haematological parameters in an endemic Nigerian cohort.

Methods

A total of 304 participants with complete microscopy and haematological data were included, comprising equal numbers of malaria-positive (n = 152) and malaria-negative (n = 152) individuals. From this cohort, an age-matched molecular subset of 40 participants (22 malaria-positive and 18 malaria-negative) was selected for rTL and hTERT analyses. Relative leukocyte telomere length was determined as the telomere-to-single-copy gene (T/S) ratio using 36B4, while hTERT expression was quantified by RT-qPCR using GAPDH as the housekeeping gene.

Results

Malaria-positive participants had significantly lower haemoglobin and platelet counts than controls (both p < 0.001). In the molecular subset, malaria-positive participants had significantly shorter rTL than controls (p < 0.001), whereas hTERT expression was significantly higher (p = 0.004). Among malaria-positive participants, rTL differed across parasite-density categories (p = 0.011) and was inversely associated with parasite density (r = −0.68, p < 0.001). Exploratory multivariable analyses showed that malaria positivity and higher parasite density were independently associated with shorter relative leukocyte telomere length.

Discussion/conclusion

To the best of our knowledge, this study is the first to provide patient-level evidence supporting the hypothesis that active malaria may contribute to the shorter relative leukocyte telomere length observed in malaria-endemic African populations. Longitudinal studies are needed to determine whether these changes are transient, cumulative, or reversible following treatment.