Aberrant leukocyte telomere length in Birdshot Uveitis

Vazirpanah, Nadia; Verhagen, Fleurieke H.; Rothova, Aniki; Missotten, Tom; Velthoven, Michelle Helena van; Hollander, Anneke I. den; Hoyng, Carel B.; Broen, Jasper; Kuiper, Jonas J.W.

doi:10.1371/journal.pone.0176175

Cited by 5 publications

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One study revealed longer TL in ocular birdshot uveitis patients compared to unrelated healthy controls. 42 These contradictory phenomena may be attributed to deleterious lifestyle, distinct cellular turnover due to chronic inflammation, and other determinants in the disease process. 3 Furthermore, the relatively small populations and low incidence of JIA-associated iridocyclitis would unquestionably result in the inconsistency of the results.…”

Section: Discussionmentioning

confidence: 99%

Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population

Zhang¹

2022

JIR

View full text Add to dashboard Cite

Background: Telomere maintenance is increasingly being considered as fundamental to the progression of immune-mediated inflammatory diseases. However, the causality underlying the purported relationship has not been fully elucidated. In the present work, we applied Mendelian randomization (MR) analysis to obtain estimates of the causal effect of telomere length (TL) on the risk of juvenile idiopathic arthritis (JIA) and JIA-associated iridocyclitis. Methods: Two-sample MR analysis was conducted using summary-level data from the largest genome-wide association studies concerning TL (78,592 individuals), JIA (6056 cases and 25,086 controls), and JIA-associated iridocyclitis (1430 cases and 9,2767 controls). All the participants were of European ancestry. The inverse variance weighted (IVW) method was applied to estimate the causal effects. Sensitivity analyses incorporating multiple complementary MR approaches were implemented to test the robustness of the association and examine potential bias from pleiotropy. Results: In our MR analysis, genetically predicted shorter TL was associated with an increased risk of JIA (IVW: odds ratio=1.68, 95% CI: 1.13-2.48, P=0.009), but not with the risk of JIA-associated iridocyclitis (IVW: odds ratio=1.75, 95% CI: 0.81-3.79, P=0.155). The other MR methods produced consistent results. Besides, a leave-one-out sensitivity analysis yielded similar findings and validated the robustness of the causal relationship. MR-Egger regression revealed no notable horizontal pleiotropy (intercept=0.046, P=0.175). Conclusion:This work provides evidence of a negative association between TL and JIA risk, but not for the association between TL and the risk of JIA-associated iridocyclitis, in a European population. Future studies with larger sample sizes are warranted to elucidate the underlying role of TL in these diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population

Zhang¹

2022

JIR

View full text Add to dashboard Cite

show abstract

“…This may result from the breakdown of proteins of the sheltered complex or related factors associated with DNA repair or recombination (32). In addition, another study comprising 91 patients with Birdshot uveitis and 150 healthy controls revealed that the Birdshot patients had longer telomeres than the healthy controls, indicating a complicated telomere biology in chronic inflammation (33). Interestingly, like AS, Birdshot uveitis patients are closely associated with HLA class I (HLA-B27) (30,31).…”

Section: Discussionmentioning

confidence: 99%

Assessing the association of leukocyte telomere length with ankylosing spondylitis and rheumatoid arthritis: A bidirectional Mendelian randomization study

et al. 2023

View full text Add to dashboard Cite

BackgroundTelomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study.MethodsLTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran’s Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome.ResultsIn the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis.ConclusionLonger LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.

show abstract