Shorter telomere length, higher telomerase activity in association with Tankyrase gene Polymorphism contribute to High-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a non-cardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high-altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High altitude pulmonary edema-patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200), and healthy-highlanders (HLs, n = 200). Variants of TNKS were genotyped using PCR-RFLP. Plasma tankyrase level was estimated using ELISA, expression of TNKS, and relative telomere length were assessed by RT-qPCR, and telomerase activity was assessed by TRAP assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (p = 0.006). TNKS was up-regulated 9.27 folds in HAPE-p (p = 1.01E-06) and down-regulated in HLs by 3.3 folds (p = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (p = 0.03) and HLs (p = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (p = 0.01) and HLs (p = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/μl) and the highest telomerase activity (0.0268 amoles/μl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.