Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema
| Autor: | V. Samuel Raj, Ramendra Pati Pandey, Ghulam Mohammad, Arpana Vibhuti, Manjula Miglani, Archana Gupta, Manjari Rain, Qadar Pasha, Tashi Thinlas |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Telomerase DNA Repair Genotype DNA damage Hypertension Pulmonary Altitude Sickness Biology law.invention 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation law Internal medicine High-altitude pulmonary edema Genetics medicine Humans Genetic Predisposition to Disease Hypoxia Molecular Biology Alleles Genetic Association Studies Genetics (clinical) Polymerase chain reaction Aged Tankyrases Altitude Telomere Homeostasis Heterozygote advantage General Medicine Middle Aged Telomere medicine.disease Pulmonary edema Healthy Volunteers 030104 developmental biology Endocrinology 030220 oncology & carcinogenesis Female Polymorphism Restriction Fragment Length DNA Damage |
| Zdroj: | Human Molecular Genetics. 29:3094-3106 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | High-altitude pulmonary edema (HAPE) is a noncardiogenic 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 highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction–restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol 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 upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated 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. |
| Databáze: | OpenAIRE |
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