The Telomere-Telomerase System Is Detrimental to Health at High-Altitude

Qadar Pasha (), Manjari Rain, Sana Tasnim, Hema Kanipakam, Tashi Thinlas and Ghulam Mohammad
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Qadar Pasha: Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
Manjari Rain: Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
Sana Tasnim: Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
Hema Kanipakam: Council of Scientific & Industrial Research-Institute of Genomics and Integrative Biology, New Delhi 110007, India
Tashi Thinlas: Department of Medicine, Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India
Ghulam Mohammad: Department of Medicine, Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India

IJERPH, 2023, vol. 20, issue 3, 1-22

Abstract: The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training.

Keywords: telomere; telomerase; high-altitude; high-altitude pulmonary edema; adaptation; genetic predisposition (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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