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Serum Anti-Inflammatory and Inflammatory Markers Have No Causal Impact on Telomere Length: A Mendelian Randomization Study Publisher



Mazidi M1 ; Shekoohi N2 ; Katsiki N3 ; Rakowski M4 ; Mikhailidis DP5 ; Banach M6, 7
Authors
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Authors Affiliations
  1. 1. Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Strand, London, United Kingdom
  2. 2. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
  4. 4. Polish Lipid Association (PoLA), Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group, Poland
  5. 5. Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, United Kingdom
  6. 6. Department of Hypertension, Department of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland
  7. 7. Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland

Source: Archives of Medical Science Published:2021


Abstract

Introduction: The relationship between inflammatory and anti-inflammatory markers and telomere length (TL), a biological index of aging, is still poorly understood. By applying a 2-sample Mendelian randomization (MR), we investigated the causal associations between adiponectin, bilirubin, C-reactive protein (CRP), leptin, and serum uric acid (SUA) with TL. Material and methods: MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on our interested exposure and TL. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method. Results: With regard to adiponectin, CRP, leptin, and SUA levels, we found no effect on TL for all 4 types of tests (all p > 0.108). Results of the MR-Egger (p = 0.892) and IVW (p = 0.124) showed that bilirubin had no effect on telomere maintenance, whereas the results of the WM (p = 0.030) and RAPS (p = 0.022) were negative, with higher bilirubin concentrations linked to shorter TL. There was a low likelihood of heterogeneity for all the estimations, except for bilirubin (IVW p = 0.026, MR Egger p = 0.018). MR-PRESSO highlighted no outlier. For all the estimations, we observed negligible intercepts that were indicative of low likelihood of the pleiotropy (all p > 0.161). The results of leave-one-out method demonstrated that the links are not driven because of single nucleotide polymorphisms (SNPs). Conclusions: Our results highlight that neither the anti-inflammatory nor pro-inflammatory markers tested have any significant causal effect on TL. The casual role of bilirubin on TL still needs to be investigated. © 2021 Termedia & Banach