Ender Coskunpinar

ANALYSIS OF SERUM MICRO-RNAs AS POTENTIAL BIOMARKER IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) as a complex disease with genetic and environmental compound is one of the leading causes of death in worldwide. This disease is characterized by lower airway inflammation, and increases risk of lung cancer in smokers. Micro-RNA (miRNA) molecules are key regulators in gene expression that have been widely associated with a several diseases. Differential expression of miRNAs is involved in lung tissue of COPD, but there is no information about biomarker potential of circulating miRNAs in patients. To analyze the miRNA expression profile in COPD, levels of serum miRNAs were profiled by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) array system. The authors examined 72 miRNAs by qRT-PCR array, in 20 COPD patients and 12 control subjects. U6snRNA was used for normalization of the expression of miRNAs for each sample. According to the results, 5 miRNAs were found to be significantly dysregulated. There was down-regulation of miR-20a, miR-28–3p, miR-34c-5p, and miR-100, and up-regulation of miR-7, compared with the controls. This was the first study in COPD for screening of serum miRNAs for searching for biomarker. These results are preliminary screening data and should be confirmed with large patient groups. If so, these miRNAs are likely being involved in pathogenesis of COPD and may give clues for designing therapeutic strategy.

The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study.

Introduction Recent studies have demonstrated the potential of microRNAs (miRNA) as biomarkers in various cardiovascular disorders. The aim of the present study was to quantitatively evaluate the expression levels of miRNAs in patients with chronic congestive heart failure (CHF) in order to identify differential expression profiles as biomarkers with prognostic values. Materials and method The study included 20 clinically stable [New York Heart Association (NYHA) II] and 22 decompensated (NYHA III and IV) CHF patients and 15 healthy controls. miRNA profiling was performed using a microarray method. Dysregulated miRNAs were evaluated for their biomarker potential. Results Microarray profiling revealed an increase in the expression of miR-21, miR-650, miR-744*, miR-516-5p, miR-1292, miR-182, miR-1228, miR-595, miR-663b, miR-1296, miR-1825, miR-299-3p, miR-662 miR-122*, miR-3148 and miR-518e* and a decrease in the expression of miR-129-3p, miR-3155, miR-3175, miR-583, miR-568, miR-30d, miR-200a-star, miR-1979, miR-371-3p, miR-155-star and miR-502-5p in sera of CHF patients. The prognostic value of miR-182 [area under the curve (AUC) 0.695] was found to be superior to pro-brain type natriuretic peptide (NT-proBNP; AUC 0.350) and high-sensitivity C-reactive protein (hs-CRP) (AUC 0.475) by receiver operator characteristic (ROC) analysis. Cox regression analysis showed that miR-182 could predict cardiovascular mortality (P = 0.032). Conclusion We demonstrated the increased expression levels of circulating miRNAs in CHF as compared with controls. Moreover, miR-182 was found to be a potential prognostic marker in CHF.

Serum anti-Müllerian hormone levels are lower in reproductive-age women with Crohn's disease compared to healthy control women

BACKGROUND AND AIM Crohns disease (CD) decreases fertility both directly, by inducing inflammation in the fallopian tubes and ovaries, and indirectly, through the surgical interventions and tubal adhesions associated with disease treatment. Anti-müllerian hormone (AMH) is a reliable indicator of ovarian reserve in women. We aimed to compare serum AMH levels between reproductive-age women with CD and healthy controls. METHODS Serum AMH levels were measured by ELISA in 35 women with CD and 35 age-matched healthy women controls. RESULTS CD patients and controls were similar in terms of age, height, weight and BMI. Mean CD duration was 60 months. CRP, ESR and leukocyte counts were significantly higher in CD patients compared to the controls (p<0.001, p=0.004 and p=0.04, respectively). AMH levels in CD patients (1.02 ± 0.72) were significantly lower compared to the controls (1.89 ± 1.80) (p = 0.009). Serum AMH levels in CD patients with active disease (0.33 ± 0.25) were significantly lower compared to CD patients who were in remission (1.53 ± 0.49) (p = 0.001). Serum AMH levels were similar in CD patients with a disease duration of less than 5 years (17 patients) and CD patients with a disease duration of greater than 5 years (18 patients) (p = 0.8). In CD patients, a negative correlation between CDAI and serum AMH levels was found (r = -0.718, p < 0.001). Serum AMH levels were similar in CD patients who had (6 patients) and had not undergone (29 patients) surgical treatment (p = 0.2). CONCLUSION Serum AMH levels of reproductive-age women with CD were significantly lower compared to the controls. CDAI and AMH are inversely correlated.

Bsmi polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men.

Background and aims: Sarcopenia is defined as a reduction in skeletal muscle mass, strength, and endurance observed with advancing age. Although Vitamin D receptor (VDR) polymorphism is reported to be associated with muscle mass and strength, evidence for this is limited and conflicting. In this study, we examined the association between the polymorphisms of VDR gene BsmI, TaqI and FokI and muscular mass and strength in elderly men. Methods: This is a cross-sectional study conducted in a university hospital. One hundred and twenty men over 65 years of age participated, all participants were active men living independently in Istanbul, who were followed as outpatients in geriatric polyclinics. Most common diagnoses were hypertension, hyperlipidemia, and mild to moderate osteoarthritis. Morbid obese patients were not included in the study. Genomic DNA was extracted from peripheral blood, and VDR genotypes were determined by the polymerase chain reaction. The peak torque of the knee flexors and extensors was measured on a Cybex 350 dynamometer. Body muscle mass was calculated by using bioelectric impedance analysis. Results: The extensor strength of the knee was higher in BB homozygotic men than in the Bb/bb group. No significant association was found with TaqI and FokI haplotypes. There was no significant association between muscle mass and strength, or between muscle mass and VDR genotype. Conclusion: Our data suggest that VDR gene BsmI polymorphism is associated with muscular strength in elderly men.

Circulating miR-221-3p as a novel marker for early prediction of acute myocardial infarction.

Recent studies have reported circulating microRNAs (miRNAs) as novel biomarkers for cardiovascular diseases including acute myocardial infarction, heart failure, diabetes mellitus, stroke, and acute pulmonary embolism. The aims of this study were 1) to compare the plasma expression levels of miRNAs in patients with acute coronary syndrome (ACS) and control subjects and in ST-elevation myocardial infarction (STEMI) and non-STEMI 2) to evaluate miRNAs potential to be used as novel diagnostic biomarkers for ACS. Twenty seven consecutive patients, admitted to emergency department of a training and research hospital between January-December 2013 with acute chest pain and/or dyspnea and diagnosed with ACS, and 16 non-ACS control subjects were included in this study. miRNA profiling was performed by using real time polymerase chain reaction. Functions of dysregulated miRNAs were evaluated by computerized-pathways analysis. miR-221-3p was one of the two most dysregulated miRNAs with a fold regulation of 3.89. It was significantly positively correlated with both Troponin and GRACE and Synthax Score. Moreover, miR221-3p was found to be significantly inversely correlated with left ventricular ejection fraction. miR-221-3p was the most prominent biomarker candidate with an area under curve (AUC) level of 0.881 (95% confidence interval: 0.774-0.987; p=0.002). The present study is the first to report an increased expression levels of miR-221-3p in AMI. Since miR-221-3p has a high discriminative value and significant relations with Troponin, GRACE and Synthax score and left ventricular systolic function, it may be a potential biomarker for early prediction of AMI.

miR-421, miR-155 and miR-650: Emerging Trends of Regulation of Cancer and Apoptosis

It is becoming progressively more understandable that between transcription and translation there lies another versatile regulator that quantitatively controls the expression of mRNAs. Identification of miRNAs as key regulators of wide ranging signaling cascades and modulators of different cell-type and context dependent activities attracted basic and clinical scientists to study modes and mechanisms in details. In line with this approach overwhelmingly increasing in vivo and in vitro studies are deepening our understanding regarding miR-421, mir-155 and miR-650 mediated regulation of cellular activities. We also attempt to provide an overview of long non coding RNAs.

Serum osteopontin levels as a predictor of portal inflammation in patients with nonalcoholic fatty liver disease

BACKGROUND Osteopontin is a secreted phosphorylated glycoprotein that is expressed by a variety of cell types and that mediates numerous and diverse biological functions. Osteopontin knockout mice are protected from obesity-induced hepatic steatosis. In the present study, we sought to investigate whether serum osteopontin concentrations are associated with liver histology in patients with nonalcoholic fatty liver disease. METHODS Serum levels of osteopontin were measured by enzyme-linked immunosorbent assay in 179 well-characterized patients with nonalcoholic fatty liver referred for liver histology and 123 control subjects. RESULTS Serum osteopontin levels were markedly higher in patients with nonalcoholic fatty liver disease than in controls (p<0.001). Multivariable analysis showed that osteopontin levels were strongly and independently associated with both portal inflammation (β=0.294, p<0.01) and serum aminotransferase levels (aspartate aminotransferase: β=0.295, p<0.01; alanine aminotransferase; β=0.285, p<0.01). CONCLUSION In summary, these data demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty liver disease and are a significant independent predictor of portal inflammation in this clinical entity.

The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease.

BACKGROUND Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case-control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed. METHODS The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR-RFLP assay. Anthropometric measurements were measured in all participants. RESULTS There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p=0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA+AA genotypes in male CHD patients (p=0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age<55 (OR=2.837, p=0.001) and TC ≥ 5.18 mmol/L (OR=1.970, p=0.027) in male subjects. However, this association was not observed in female patients (p>0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age<55 years. CONCLUSION These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.

Is MMP-7 Gene Polymorphism a Possible Risk Factor for Chronic Obstructive Pulmonary Disease in Turkish Patients

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This study was performed to test the association between MMP-7 (rs155668818) and MMP-12 (rs56184183) polymorphisms in the MMP-7 gene and COPD risk and its severity in the Turkish population. MMP-7 and MMP-12 polymorphisms were genotyped in 85 patients with COPD and 73 healthy control subjects using real-time polymerase chain reaction analysis. There were significant differences in the distribution of MMP-7 genotypes but not in the frequencies of these alleles between COPD patients and controls (p=0.009, p=0.102, respectively). The MMP-7 AA genotype was found to be associated with an increased risk of COPD (p=0.004; odds ratio: 2.576; confidence interval: 1.297-5.119). The lowest values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC in patients with GG homozygosity were determined and these values were statistically significant compared to the control subjects (p<0.001, p<0.001, p<0.001). When the present study groups were analyzed for MMP-12 polymorphism, it was found that all the subjects had wild-type genotype for this polymorphism. These findings have suggested that MMP-7 polymorphism might be associated with the risk and progression of COPD in the Turkish population.

Investigation of a Possible Relationship Between EPHX1 Gene Polymorphisms and Colorectal Cancer in Turkish Society

Metabolism of chemical carcinogens, including their activation and detoxification, plays a key role in carcinogenesis. Microsomal epoxide hydrolase (EPHX1) has an important role in the metabolism of polycyclic aromatic hydrocarbons and detoxification of procarcinogens. The aim of this study was to investigate the association between colorectal cancer (CRC) development and EPHX1 gene polymorphisms. We investigated the polymorphisms in exon 3 (T>C, Tyr113His) and exon 4 (A>G, His139Arg) of the EPHX1 gene in 68 CRC patients and 116 controls by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the Try113Try, Try113His, and His113His for EPHX1 exon 3 were 37.9%, 55.2%, and 6.9% in controls and 39.7%, 42.6%, and 17.6% in CRC patients, respectively. Frequencies of EPHX1 exon 4 genotypes were 62.1% His139His, 37.9% His139Arg, and 0% Arg139Arg in the control group and 76.5% His139His, 22.1% His139Arg, and 1.5% Arg139Arg in the patient group. Individuals carrying the EPHX1 exon 3 His113His genotype had a 2.5-fold increased risk (p=0.024), and those carrying the EPHX1 exon 4 His139Arg genotype had decreased risk of CRC compared with controls (p=0.019). Even though exon 3 Tyr113His and exon 4 His139Arg polymorphisms for EPHX1 gene appear to be important factors for CRC risk, further investigations with larger study groups are needed to fully elucidate the role of these polymorphisms in the development of CRC.