Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients

Eftekharian, Mohammad Mahdi; Ghafouri‐Fard, Soudeh; Soudyab, Mohammad; Omrani, Mir Davood; Rahimi, Mehrali; Sayad, Arezou; Komaki‬, Alireza; Mazdeh, Mehrdokht

doi:10.1007/s12031-017-0982-1

Cited by 63 publications

(47 citation statements)

References 19 publications

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“…For example, the SNP rs2013208 showed a strong association with coronary artery disease,12 and a correlation between disability progression in MS and increased risk of coronary artery disease has been shown in a case–control study 35. Also, rs2013208 is located within an intron of the gene RBM5 , which encodes a long non-coding RNA binding protein whose aberrant expression has been implicated as an underlying driver of MS causation 36. The SNP rs17173637, located within an intron of TMEM176A , is significantly upregulated in whole blood samples of people with MS 37.…”

Section: Discussionmentioning

confidence: 99%

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis

Zhang

Zhou

Mei

et al. 2019

J Neurol Neurosurg Psychiatry

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ObjectiveTo investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).MethodsThe association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p<0.05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression.ResultsFive lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (ptrend=1.4×10−6), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL; pinteraction=0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL; pinteraction=0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL.InterpretationIn this prospective cohort study, both lipid levels and lipid-related polymorphisms individually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.

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Section: Discussionmentioning

confidence: 99%

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis

Zhang

Zhou

Mei

et al. 2019

J Neurol Neurosurg Psychiatry

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“…For instance, lnc-THRIL is upregulated in multiple sclerosis patients compared with healthy controls. 15 And lnc-THRIL is clearly lower in the acute phase compared with convalescent-phase in patients with Kawasaki disease. 9 The close association of lnc-THRIL with Kawasaki disease and multiple sclerosis as well as its correlation with TNF-α implicate that it may be involved in other inflammatory diseases, while it is not studied in sepsis yet.…”

Section: Subgroup Analysismentioning

confidence: 86%

“…There have been only a few studies revealing the aberrant expression and function of lnc‐THRIL in patients with inflammatory and auto‐immune diseases. For instance, lnc‐THRIL is upregulated in multiple sclerosis patients compared with healthy controls . And lnc‐THRIL is clearly lower in the acute phase compared with convalescent‐phase in patients with Kawasaki disease .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

Wang

et al. 2019

Clinical Laboratory Analysis

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BackgroundThis present study aimed to investigate the correlation of long non‐coding RNA THRIL (lnc‐THRIL) with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation, and mortality in sepsis patients.MethodsA total of 109 sepsis patients admitted to intensive care units were consecutively recruited, and their blood samples were collected. After admission, patients were supervised and screened daily to identify the occurrence of ARDS. Clinical characteristics, routine laboratory testing, and disease severity were recorded, and all enrolled patients were followed up until death in the hospital or discharge for mortality records. Lnc‐THRIL was detected by quantitative polymerase chain reaction, and inflammatory cytokine levels were measured by human enzyme‐linked immunoassay.ResultsA total of 32 (29.4%) sepsis patients occurred ARDS and 77 (71.6%) did not. Lnc‐THRIL was upregulated in ARDS group compared with non‐ARDS group, and it had good value in distinguishing ARDS from non‐ARDS in sepsis patients (AUC: 0.706; 95%CI: 0.602‐0.809). Besides, lnc‐THRIL, smoke, and chronic obstructive pulmonary disease independently predicted increased risk of ARDS. As for disease severity, lnc‐THRIL positively correlated with APACHE II score and SOFA score in sepsis patients. Regarding inflammation, lnc‐THRIL was positively associated with CRP, PCT, TNF‐α, and IL‐1β levels in sepsis patients. Additionally, the mortality rate was 30.2%, and lnc‐THRIL was upregulated in non‐survivors compared with survivors, presenting a good value (AUC: 0.780; 95%CI: 0.683‐0.876) in predicting mortality in sepsis patients.ConclusionLnc‐THRIL predicts increased risk of ARDS and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

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“…2 Genome-wide association studies have revealed numerous MS risk loci in the neighborhood of immune response-related genes. 4 Based on the underscored role of long non-coding RNAs (lncRNAs) in epigenetic regulation of gene expression, these kinds of transcripts are regarded as putative markers in MS. 5 LncRNAs are transcripts with sizes longer than 200 nucleotides and no obvious open reading frames. 4 Based on the underscored role of long non-coding RNAs (lncRNAs) in epigenetic regulation of gene expression, these kinds of transcripts are regarded as putative markers in MS. 5 LncRNAs are transcripts with sizes longer than 200 nucleotides and no obvious open reading frames.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA AFAP1‐AS1 is upregulated in a subset of multiple sclerosis patients

Mazdeh

Eftekharian

Komaki‬

et al. 2019

Clinical & Exp Neuroim

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Objective Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Although the exact mechanism of this autoimmune disorder has not yet been identified, several protein coding genes and noncoding transcripts have been shown to be dysregulated in MS patients. Methods In the current study, we assessed expression of actin filament associated protein 1 (AFAP1) and its naturally occurring antisense (actin filament associated protein 1-antisense 1: AFAP1-AS1) in the peripheral blood of MS patients and healthy individuals. Results AFAP1-AS1 was upregulated in male MS patients compared with healthy male controls (P = 0.048). AFAP1 expression was not different between MS patients and controls or between any subgroups of patients and controls. The interaction between disease status and sex was significant in AFAP1-AS1 expression. There was a significant inverse correlation between expression levels of AFAP1 and AFAP1-AS1 in healthy individuals (r = À0.472, P = 0.001), but not MS patients (r = À0.251, P = 0.078). Conclusions The current study implies the role of AFAP1-AS1 dysregulation in the pathogenesis of a certain group of MS patients. Future studies are required to elaborate the underlying mechanism of such dysregulation.

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Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients

Cited by 63 publications

References 19 publications

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis

Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

Long non‐coding RNA AFAP1‐AS1 is upregulated in a subset of multiple sclerosis patients

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