Mazidi Mohsen, Shekoohi Niloofar, Katsiki Niki, Rakowski Michal, Mikhailidis Dimitri P, Banach Maciej
Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Strand, London, UK.
Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Arch Med Sci. 2021 Apr 21;17(3):739-751. doi: 10.5114/aoms/119965. eCollection 2021.
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.
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.
With regard to adiponectin, CRP, leptin, and SUA levels, we found no effect on TL for all 4 types of tests (all > 0.108). Results of the MR-Egger ( = 0.892) and IVW ( = 0.124) showed that bilirubin had no effect on telomere maintenance, whereas the results of the WM ( = 0.030) and RAPS ( = 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 = 0.026, MR Egger = 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 > 0.161). The results of leave-one-out method demonstrated that the links are not driven because of single nucleotide polymorphisms (SNPs).
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.
炎症和抗炎标志物与端粒长度（TL）（一种衰老的生物学指标）之间的关系仍未得到充分理解。通过应用两样本孟德尔随机化（MR）方法，我们研究了脂联素、胆红素、C反应蛋白（CRP）、瘦素和血清尿酸（SUA）与TL之间的因果关联。
通过使用有史以来对我们感兴趣的暴露因素和TL进行的最大规模全基因组关联研究（GWAS）的汇总数据来实施MR。应用了逆方差加权法（IVW）、基于加权中位数（WM）的方法、MR-Egger法、MR稳健调整轮廓评分（RAPS）和MR多效性残差总和与异常值（PRESSO）法。使用留一法进行敏感性分析。
关于脂联素、CRP、瘦素和SUA水平，我们发现所有4种测试类型对TL均无影响（所有P值>0.108）。MR-Egger法（P值 = 0.892）和IVW法（P值 = 0.124）的结果表明胆红素对端粒维持没有影响，而WM法（P值 = 0.030）和RAPS法（P值 = 0.022）的结果为阴性，即胆红素浓度越高，TL越短。除胆红素外（IVW法P值 = 0.026，MR-Egger法P值 = 0.018），所有估计的异质性可能性都很低。MR-PRESSO法未发现异常值。对于所有估计，我们观察到截距可忽略不计，这表明多效性的可能性很低（所有P值>0.161）。留一法的结果表明这些关联不是由单核苷酸多态性（SNP）驱动的。
我们的结果表明，所测试的抗炎和促炎标志物对TL均无显著因果效应。胆红素对TL的因果作用仍需进一步研究。
