Circulating biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy assessed by cardiac magnetic resonance

Abstract

Background: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice.

Objective: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM.

Methods: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis.

Results: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r?=?0.32, p?=?0.012), LV mass indexed for the body surface area (LVMI) (r?=?0.27, p?=?0.036) and maximal wall thickness (MWT) (r?=?0.31, p?=?0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r?=?0.58, p?<?0.0001), LVMI (r?=?0.48, p?=?0.0001), MWT (r?=?0.31, p?=?0.015) and late gadolinium enhancement (LGE) mass (r?=?0.37, p?=?0.003). There were positive correlations between NT-proBNP levels and LVM (r?=?0.33, p?=?0.01), LVMI (r?=?0.41, p?=?0.001), MWT (r?=?0.42, p?<?0.001) and LGE mass (r?=?0.44, p?<?0.001).

Conclusions: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.     

Evaluation of mediators of oxidative stress and inflammation in patients with acute appendicitis

Context: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA).

Methods: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed.

Results: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p?<?0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p?=?0.29), CAT (p?=?0.19), or TBARS levels (p?=?0.18), whereas protein carbonyls presented significant increase (p?<?0.0001).

Conclusion: Evaluating these biomarkers could aid in diagnosing AA.     

Association between circulating microRNA-126 expression level and tumour necrosis factor alpha in healthy smokers

Introduction: Smoking contributes to the death of a million people worldwide each year. Smokers experience an alteration in tumour necrosis factor-alpha (TNF-α), and the risk of expected lung cancer. The study aimed at investigating the expression levels of mir-126 and mir-124, as well as TNF-α as possible biomarkers of expected smoking-related diseases.

Methods: Twenty-five male smokers’ age and sex-matched with 25 non-smokers were recruited for the present study. Plasma expression levels of mir-126 and mir-124 were evaluated using quantitative real-time PCR. Lipid profile, TNF-α, interleukin-6 and C-reactive protein were assessed in plasma of each participant.

Results: Plasma miR-126 was statistically down-regulated in smokers relative to non-smokers; however, mir-124 did not show any significant changes between groups. Among the measured parameters, mir-126 and tumour necrosis factor alpha (TNF-α) displayed a good discrimination and sensitivity between smokers and non-smokers (AUC = 0.809 (95% CI: 0.668–0.95; p?<?0.001) and 0.742(95% CI: 0.584–0.9; p?<?0.01), respectively. Also, the combined evaluation of miR-126 and TNF-α levels showed high discrimination (AUC= 0.889 (95% CI: 0.779–1.00; p?<?0.0001), sensitivity = 85%, and specificity = 80% in the diagnosis of smokers with non-smokers.

Conclusions: MiR-126 and TNF-α are potential biomarkers of smoking-related diseases and are important in assessing the expected tobacco-related harm.     

Changes of urinary phospholipids in the chronic kidney disease patients

Abstract

Objective: To evaluate whether urinary phospholipids could be regarded as biomarkers of chronic kidney disease.

Materials and methods: Thirteen healthy volunteers and 26 consecutive chronic kidney disease patients were included. Urinary phospholipids were quantified by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Results: Urinary phosphatidylcholines concentrations (PC 16:0/16:0, 16:0/22:3, 16:0/18:1 and 16:0/18:2) were significantly higher both in glomerulonephritis group (all p?<?0.001) and in tubulointerstitial injury group (all p?<?0.05) than in healthy control group. Meanwhile, sphingomyelin concentrations (SM 18:1/16:0 and 18:1/18:0) in glomerulonephritis group were significantly higher than those in healthy control group (all p?<?0.001). Urinary PCs and SMs were positively correlated with proteinuria but negatively correlated with serum albumin. Meanwhile, PCs were positively correlated with serum creatinine.

Conclusion: Our work first demonstrated that urinary phospholipids might be biomarkers for the chronic kidney disease patients. Increased urinary phospholipids in chronic kidney disease patients might result from proteinuria, damaged kidney function or proteinuria induced hypoalbuminemia or lipotoxicity.     

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p?p?p?p?Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.     

Association between gestational diabetes and biomarkers: a role in diagnosis

Background: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM.

Methods: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM.

Results: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p?=?0.04) and had more clinical risk factors (p?=?0.008). We found a significant difference in fasting insulin (p?p?=?0.046), HOMA (p?p?Conclusions: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.     

No association between the vitamin D pathway gene polymorphisms and bone biomarkers response to calcium and low dose calcitriol supplementation in postmenopausal Chinese women: a one-year prospective study

Abstract

Introduction: The aim of the study was to explore the association between the vitamin D pathway gene variations and the bone biomarkers response to calcium and low dose calcitriol supplementation in postmenopausal Chinese women.

Methods: A total of 110 healthy postmenopausal Chinese women (61.51?±?6.93?years) were enrolled. The participants were supplemented with calcium (600?mg/d) and calcitriol (0.25?μg/d), for 1?year. Four biomarkers, serum levels of beta C-terminal cross-linked telopeptides of type I collagen (β-CTX), amino-terminal propeptide of type I collagen (P1NP), parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] were measured at baseline and 12-month follow-up. Multivariate regression models were established to explore the statistical association between the change rate of the four biomarkers and 15?key genes within the vitamin D metabolic pathway.

Results: This exclusion process left 98 participants for analysis. Serum levels of P1NP, β-CTX and PTH were significantly decreased at the 12-month follow-up (all p?<?0.05). Serum 25(OH)D level had no significant change (p?>?0.05). No association was found between the vitamin D pathway gene polymorphisms and bone biomarkers response to calcium and low dose calcitriol supplementation.

Conclusions: Genetic background of postmenopausal Chinese women might not influence supplemental response of the biomarkers to calcium and low dose calcitriol.     

Biomarkers of exposure and potential harm in adult smokers of 3–7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers

Abstract

The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0–6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F_2α (8-epi-PGF_2α) and 11-dehydro-thromboxane B₂ (11-dehydro-TxB₂) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus??1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl^?1 (p=0.05), fibrinogen 292 versus 248 mg dl^?1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl^?1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl^?1 (p=0.18), urine 8-epi-PGF_2α 1935 versus 1034 pg mg^?1 creatinine (p<0.001) and urine 11-dehydro-TxB₂ 973 versus 710 pg mg^?1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.     

Neuroglobin and Nogo-a as biomarkers for the severity and prognosis of traumatic brain injury

Abstract

Objective: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis.

Methods: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96?h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed.

Results: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient’s GCS score on admission (p?<?0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p?<?0.05).

Conclusions: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

Trial registration: ClinicalTrials.gov identifier: NCT02229643.     

Dynamic thiol/disulphide homeostasis as indicator of oxidative stress in automotive workers

Abstract

Purpose: To examine thiol-disulphide homeostasis auto painters.

Materials and methods: A total of 115 male workers, including 60 auto painters workers and 55 reference group, of the painting and assembly line units respectively, were included in the study. Thiol-disulphide parameters and ischaemia-modified albumin (IMA) of groups were determined. Urinary hippuric acid, (HA) phenol, hexanedione, trichloroacetic acid, arsenic and blood lead and manganese were analysed.

Results: The median urinary HA level was significantly higher in auto painters when compared to the reference group [(2461 (1212) vs. 520 (513) µgr/L), (p?<?0.001)] . The mean disulphide level [19.7 (4.3) vs 0.15.1(4.1) μmol/L, (p?<?0.001)], the disulphide/native thiol ratio [4.72 (1.47) vs. 3.13 (1.21, (p?<?0.001)] and the disulphide/total thiol ratio [4.31 (1.23) vs. 2.94 (1.06), (p?<?0.001)] were higher in auto painters when compared to the reference group. There was a statistically significant positive correlation between urinary HA and disulphide concentrations (r?=?0.536 and p?<?0.001), disulphide/native thiol ratio (r?=?0.564 and p?<?0.001) and the disulphide/total thiol ratio (r?=?0.564 and p?<?0.001) and IMA (r?=?0.396 and p?<?0.001).

Conclusion: The results presented in this study showed that oxidative stress can be associated with occupational exposure to toluene denoted by alteration of thiol disulphide homeostasis and ischaemia-modified albumin levels.     

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet’s disease

Abstract

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.

Method: This was a case–control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.

Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p?<?0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p?<?0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p?<?0.05).

Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.     

Low proportions of folic acid deficiency after introduction of mandatory folic acid fortification in remote areas of northern Queensland,Australia: a secondary health data analysis

Abstract

Background: Australia implemented mandatory folic acid fortification of bread-making flour in 2009.

Objective: To assess the impact of folic acid fortification in remote vs. regional urban areas and Indigenous vs. non-Indigenous populations in northern Queensland.

Methods: Routinely collected data on folic acid measurements in remote areas and two regional urban centres in northern Queensland between 2004 and 2015 were analysed (n?=?13,929) dichotomously (folic deficient vs. non-deficient).

Results: Overall prevalence of folic acid deficiency was 3.2% (235/7282) in urban centres compared with 7.2% (480/6647) in remote areas (p?<?0.001), and 9.3% (393/4240) in the Indigenous population compared with 3.2% (273/8451) in the non-Indigenous population (p?<?0.001). Prevalence of folic acid deficiency dropped from 12.2% (n?=?481) in 2004–2008 to 1.5% (n?=?126) in 2010–2015 (p?<?0.001). This translates into a relative risk reduction (RRR) of 88%. RRR was 79% (7.2% vs. 1.5%) in urban centres, 91% (17.3% vs. 1.5%) in remote areas, 92% (20.5% vs. 1.6%) in the Indigenous population and 80% (7.4% vs. 1.5%) in the non-Indigenous population (p?<?0.001 for all).

Conclusions: Substantial declines of folic acid deficiency to low and comparable proportions in former high-risk populations indicate that mandatory folic acid fortification of flour has had a population-wide benefit in northern Queensland.     

Multi-biomarker analysis in patients after transcatheter aortic valve implantation (TAVI)

Abstract

Background: In this study we sought to examine whether transcatheter aortic valve implantation (TAVI) is followed by a change in the plasma levels of novel cardiovascular biomarkers.

Methods: We collected blood samples of 79 patients with severe aortic valve stenosis undergoing TAVI before and at 7 days, 1 month, 3 months and 6 months post TAVI and analyzed the plasma concentrations of GDF-15, H-FABP, fetuin-A, galectin 3, sST2 and suPAR by means of ELISA.

Results: There was a significant increase in the concentration of fetuin-A (median: 52.44 mg/ml to 113.2 mg/ml, p?<?0.001) and a significant decrease of H–FABP after TAVI (median: 4.835 ng/ml to 2.534 ng/ml, p?<?0.001). The concentrations of suPAR and sST2 showed an initial increase (suPAR median: 2755 pg/ml 3489 pg/ml, p?<?0.001; sST2 median: 5832 pg/ml to 7137 pq/ml, p?<?0.001) and subsequently decreased significantly.

Conclusion: We hypothesize that the decrease of H-FABP and the increase of fetuin-A could be due to a hemodynamic improvement after valve replacement. The initial increase of suPAR could indicate an inflammatory stimulus and the significant increase in sST2 could be due to the mechanical strain caused by implantation of the valve.     

Duration of exposure to environmental carcinogens affects DNA-adduct level in human lymphocytes

Background and objective: An important issue in human biomonitoring is determining how exposure duration affects the kinetics of molecular biomarkers. In this study we compare the influence of exposure variables on DNA adducts.

Methods: DNA adducts were analysed by 32P-postlabelling in lympho/monocytes of 677 Caucasian subjects.

Results: After correction for other variables, DNA adducts increased depending on the length of occupational and smoke exposures. Higher DNA adducts were detected in workers with more than 14 years of exposure than in workers with shorter exposures (RR?=?1.19, p?=?0.049) and in smokers with more than 10 years of exposure than in smokers with shorter exposure (RR?=?1.21, p <0.001).

Conclusions: Exposure length is the primary factor affecting DNA-adduct level in lympho/monocytes both in smokers and in occupationally exposed subjects.     

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism

Abstract

Background: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism.

Methods: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography.

Results: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p?<?0.001 and p?=?0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p?<?0.001) and positively correlated with fT3 (p?<?0.001), fT4 (p?<?0.001) and TSH receptor antibody (p?=?0.002) levels and EFT (p?=?0.001). In multivariate linear regression analysis, TSH (β?=??0.475, p?<?0.001) and EFT (β?=?0.290, p?=?0.023) levels were significantly associated with serum irisin levels.

Conclusions: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.     

Methylated arginines and nitric oxide in end-stage renal disease: impact of inflammation,oxidative stress and haemodialysis

Abstract

Objectives: To determine whether inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde, MDA) or haemodialysis (HD) affect associations between asymmetric (ADMA), symmetric (SDMA) dimethylarginine, NG-monomethyl-L-arginine (L-NMMA) and nitrite/nitrate (NOx) in end-stage renal disease (ESRD).

Method: Metabolites were measured pre-HD, after 1 hour and end-HD in 40 ESRD patients (age 63?±?14 years).

Results: Positive associations between NOx and ADMA (p?=?0.04), SDMA (p?<?0.001) and L-NMMA (p?=?0.04) were observed pre-HD. Associations weakened during HD but were not significantly influenced by CRP or MDA.

Conclusions: HD, oxidative stress or inflammation did not significantly affect the positive associations between methylated arginines and NOx in ESRD.     

Pneumoproteins and markers of inflammation and platelet activation in the blood of grain dust exposed workers

Abstract

Purpose: To investigate if blood biomarkers could indicate early signs of lung damage or cardiovascular risk due to exposure to grain dust.

Materials and methods: Pneumoproteins and markers of inflammation and platelet activation were analysed in blood samples of 102 grain elevator and compound feed mill workers. Differences between exposed (n?=?67) and controls (n?=?35), and associations with exposure measurements and respiratory health were investigated by multiple linear regression analyses.

Results: Concentrations of CC-16 and IL-6 were higher in exposed workers compared with controls (p?<?0.001 for both), whereas fibrinogen was lower (p?=?0.005). Concentrations of CRP, TNF-α, sCD40L and sP-selectin were similar in both groups. Serum CC-16 was significantly higher in workers with farm childhood, regardless of exposure. The impact of farm childhood on CC-16 interacted with smoking. None of the biomarkers were associated with exposure measurements or any of the tested respiratory health parameters.

Conclusion: Dust exposure induced inflammatory and anti-inflammatory reactions, but did not induce systemic inflammation and had no effect on platelet activation. No cause–effect relationship could be established in spite of relatively high exposure levels, particularly to endotoxin. Whether increased serum CC-16 is an early sign of lung damage or a reversible defense reaction remains unclear.     

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

Serum creatine is not a reliable marker of muscular fitness in young adults

Purpose: Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3?±?2.6?years), while controlling for age, gender, fat-free mass and biomarkers of creatine metabolism as effect modifiers.

Materials and methods: Serum creatine, creatinine and guanidinoacetic acid (GAA) levels were measured with liquid chromatography-tandem mass spectroscopy, while handgrip strength was assessed with a hydraulic hand dynamometer.

Results: Hierarchical multiple regression revealed that our model as a whole explained 79.9% of the variance in handgrip strength (p?p?p?>?0.05).

Conclusions: Having higher blood creatine appears to be unrelated with better physical performance in young healthy adults. Serum creatine was not a reliable marker of muscular fitness in this population.     

Gene expression profiling of peripheral blood leukocytes identifies potential novel biomarkers of chronic obstructive pulmonary disease in current and former smokers

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with associated systemic effects.

Objective: To use gene expression microarrays in peripheral blood leukocytes of current and former cigarette smokers to identify differences associated with COPD.

Materials and methods: Random forest modelling and a split-sample case–control approach were used to identify candidate predictors.

Results: We identified 1013 genes and one smoking exposure variable that differentiated current and former smokers with or without COPD. This predictor set was reduced to a nine-gene classifier (IL6R, CCR2, PPP2CB, RASSF2, WTAP, DNTTIP2, GDAP1, LIPE and RPL14).

Conclusion: These gene expression profiles represent potential biomarkers for COPD and may help increase mechanistic understanding of the disease.