Telomere Length of Individual Chromosomes in Patients with Rheumatoid Arthritis

Блинова, Е. А.; Зиннатова, Е В; Barkovskaya, M. Sh.; Борисов, В. И.; Сизиков, А. Э.; Kozhevnikov, V. S.; Rubtsov, N. B.; Козлов, В. А.

doi:10.1007/s10517-016-3308-3

Cited by 13 publications

(6 citation statements)

References 13 publications

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“…For parts of IMIDs, our findings were similar to those from some previous studies, while for other IMIDs, they were the opposite. The results from the MR study based on data from the FinnGen Biobank corroborate the findings of retrospective studies that show shorter LTL is a risk factor for RA (Blinova et al, 2016;Gamal et al, 2018;Lee and Bae, 2018), SS (Kawashima et al, 2011;Noll et al, 2020), sarcoidosis (Maeda et al, 2009;Afshar et al, 2021), IPF (McDonough et al, 2018;Ley et al, 2020), and psoriasis (Liu et al, 2008). Furthermore, our results are also similar to previously reported MR studies of LTL and the risk of RA (Zeng et al, 2020) and IPF (Duckworth et al, 2021).…”

Section: Comparison With Previous Studiessupporting

confidence: 77%

Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

et al. 2023

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Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10−4), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10−5), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10−6), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10−3), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10−4), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10−7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10−4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10−5).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.

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Section: Comparison With Previous Studiessupporting

confidence: 77%

Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

et al. 2023

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“…[35] Somatic chromosomal aberrations have been reported as a genetic feature in several chronic rheumatic diseases. [12,13,33] In the current study, we observed that arthritis induced an increase in the occurrence of aneuploid sperm, and the elevations were significantly higher in disomies (Table 1). Nevertheless, compared with control animals, no significant increase was found in the frequency of total diploid sperm in arthritic mice.…”

Section: Discussionsupporting

confidence: 60%

“…There have been numerous studies showing the occurrence of numerical and structural chromosomal abnormalities associated with the disease severity and duration in patients with rheumatic disorders. [ 12,13 ] These findings show that chromosomal aberrations may reflect the pathogenesis of chronic inflammatory stress in rheumatic diseases. The increased disease activity necessitates intensive therapy with disease‐modifying antirheumatic drugs, including biological therapy.…”

Section: Introductionmentioning

confidence: 88%

Rituximab alleviates increased disomic sperm in DBA/1J mouse models of rheumatoid arthritis via restoration of redox imbalance

Attia

Al-Hamamah

Attia

et al. 2023

J Biochem & Molecular Tox

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Compared to the general population, patients with arthritis have a higher risk of fertility abnormalities, which have deleterious effects on both reproductive function and pregnancy outcomes, especially in patients wishing to conceive. These may be due to the disease itself or those of drug therapies. Despite the increasing use of rituximab in arthritis, limited data are available on its potential to induce aneuploidy in germ cells. Therefore, the aim of the current investigation was to determine if repeated treatment with rituximab affects the incidence of aneuploidy and redox imbalance in arthritic mouse sperm. Mice were treated with 250 mg/kg rituximab once weakly for 3 weeks, and then sperm were sampled 22 days after the last dose of rituximab. Fluorescence in situ hybridization assay with chromosome‐specific DNA probes was used to evaluate the disomic/diploid sperm. Our results showed that rituximab had no aneuploidogenic effect on the meiotic stage of spermatogenesis. Conversely, arthritis induced a significantly high frequency of disomy, and treatment of arthritic mice with rituximab reduced the increased levels of disomic sperm. The occurrence of total diploidy was not significantly different in all groups. Reduced glutathione and8‐hydroxydeoxyguanosine, markers of oxidative stress were significantly altered in arthritic animals, while rituximab treatment restored these changes. Additionally, arthritis severity was reduced after rituximab treatment. We conclude that rituximab may efficiently alleviate the arthritis‐induced effects on male meiosis and avert the higher risk of abnormal reproductive outcomes. Therefore, treating arthritic patients with rituximab may efficiently inhibit the transmission of genetic anomalies induced by arthritis to future generations.

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“…Moreover, quantitative fluorescence in situ hybridization (Q-FISH) on metaphase chromosomes in the PB lymphocytes showed that the distribution of TEL for individual chromosomes differs in normal and pathological conditions. Patients with rheumatoid arthritis had significantly shorter telomeres of chromosome 4p, an observation that could be related to the pathology of the disease, while the activity of the disease is inversely correlated with the length of the telomeres of the 10p chromosome which carries the genes involved in the differentiation and proliferation of T-cells ( 44 ). The dynamic activity of telomerase is correlated with the action of an acute stressor and with two types of reactions to stress-psychological stress and neuroendocrine (cortisol) responses to the stressor ( 24 ).…”

Section: Telomerase Activity and Agingmentioning

confidence: 99%

Telomerase and telomeres in aging theory and chronographic aging theory (Review)

et al. 2020

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The current review focuses on the connection of telomerase and telomeres with aging. in this review, we describe the changes in telomerase and telomere length (Tel) during development, their role in carcinogenesis processes, and the consequences of reduced telomerase activity. More specifically, the connection of Tel in peripheral blood cells with the development of aging-associated diseases is discussed. The review provides systematic data on the role of telomerase in mitochondria, the biology of telomeres in stem cells, as well as the consequences of the forced expression of telomerase (telomerization) in human cells. additionally, it presents the effects of chronic stress exposure on telomerase activity, the effect of Tel on fertility, and the effect of nutraceutical supplements on Tel. Finally, a comparative review of the chronographic theory of aging, presented by olovnikov is provided based on currently available scientific research on telomere, telomerase activity, and the nature of aging by multicellular organisms. Contents 1. introduction 2. Telomeres and telomerase: The generation of aging theory 3. Telomerase activity and aging 4. chronographic theory of aging: neural chronograph 5. conclusions and future research directions

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Telomere Length of Individual Chromosomes in Patients with Rheumatoid Arthritis

Cited by 13 publications

References 13 publications

Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

Rituximab alleviates increased disomic sperm in DBA/1J mouse models of rheumatoid arthritis via restoration of redox imbalance

Telomerase and telomeres in aging theory and chronographic aging theory (Review)

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