Diagnostic fondé sur un modèle quantitatif

Traité IC2, Série Systèmes Automatisés. Ed. Hermès Sciences, 16 mars 2007. ISBN-13: 978-2746214108International audienc

Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. METHODOLOGY: To address this issue we have measured in the blood leucocytes of MDD patients (N=17) and controls (N=16) the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a) and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1), telomere regulation and elongation (TERT), and in the response to biopsychological stress (FOS and DUSP1). RESULTS: The OGG1, p16(INK4a), and STMN1 gene were significantly up-regulated (25 to 100%) in the leucocytes of MDD patients. Expression of p16(INK4a) and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a), STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls). Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. CONCLUSIONS: Expression of p16(INK4) and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population

Germline JAK2 L611S mutation in a child with thrombocytosis

IF 9.090 (2017)International audienc

Characteristics of the Depressed and Control Subjects.

<p>Characteristics of the Depressed and Control Subjects.</p

The mean and standard deviation (inter-individual variability) of the Ct values in the depressed and control group. The I-WV value is the mean of the inter-well Ct variation (triplicate runs).

<p>The mean and standard deviation (inter-individual variability) of the Ct values in the depressed and control group. The I-WV value is the mean of the inter-well Ct variation (triplicate runs).</p

Correlative pattern of gene expression (Pearson's coefficient) in the blood leucocytes of controls and MDD subjects. For each gene the |r| value of control subjects (when significant) is in normal font weight on the upper row, and the |r| of the depressed patients in bold font weight on the lower row.

<p>Correlative pattern of gene expression (Pearson's coefficient) in the blood leucocytes of controls and MDD subjects. For each gene the |r| value of control subjects (when significant) is in normal font weight on the upper row, and the |r| of the depressed patients in bold font weight on the lower row.</p

Adjustment curves of the linear regression analysis showing the direct correlation between the expression level of p16^INK4 (F = 15.68, R² = 0.51, p = 0.001) and STMN1 (F = 12.54, R² = 0.45, p = 0.003) and the anxiety scores (HAM-A scale).

<p>Adjustment curves of the linear regression analysis showing the direct correlation between the expression level of p16^INK4 (F = 15.68, R² = 0.51, p = 0.001) and STMN1 (F = 12.54, R² = 0.45, p = 0.003) and the anxiety scores (HAM-A scale).</p

Sequences and localization on the CDS reference sequence (NCBI) of the forward (F) and reverse (R) primers used in the Q-PCR technique.

<p>Sequences and localization on the CDS reference sequence (NCBI) of the forward (F) and reverse (R) primers used in the Q-PCR technique.</p

Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease.

International audienceOBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. METHODS: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N = 85), past smokers (PS) (N = 78) and never smokers (NS) (N = 76). RESULTS: NS had a higher risk profile including hypertension, and CS were younger than PS and NS (-13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861 AU, respectively; p = 0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS + NS) was the strongest predictor of the c-Fos transcript level, (B = 0.042 ± 0.014, p = 0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI). CONCLUSION: Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c-Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease

Circulating leukocyte telomere length and oxidative stress: A new target for statin therapy

International audienc