Disease Markers - Volume 27, issue 6

Authors: Boštjančič, Emanuela | Zidar, Nina | Glavač, Damjan

Article Type: Research Article

Abstract: MicroRNAs (miRNAs), small non-coding RNA molecules, are negative regulators of gene expression. Recent studies have indicated their role in various forms of cardiovascular disease. In spite of the number of miRNA microarray analyses performed, little is known about the genome-wide miRNA expression pattern in human myocardial infarction (MI). Using miRNA microarrays and bioinformatic analysis, miRNA expression was analyzed on human MI and foetal hearts compared to healthy adult hearts, to determine whether there is any …similar expression pattern between MI and foetal hearts, and to identified miRNAs that have not previously been described as dysregulated in cardiovascular diseases. Of 719 miRNAs analyzed, ∼ 50% were expressed in human hearts, 77 miRNAs were absent from all tested tissues and 57 were confidently dysregulated in at least one tested group. Some expression patterns appeared to be similar in MI and foetal hearts. Bioinformatic analysis revealed 10 miRNAs as dysregulated in MI not yet related to cardiovascular disease, and 5 miRNAs previously described only in animal models of cardiovascular diseases. Finally, qRT-PCR analysis confirmed dysregulation of 7 miRNAs, miR-150, miR-186, miR-210, miR-451, and muscle-specific, miR-1 and miR-133a/b; all of these are believed to be involved in various physiological and pathological processes. Show more

Keywords: MiRNA, microarray, myocardial infarction, expression

DOI: 10.3233/DMA-2009-0671

Citation: Disease Markers, vol. 27, no. 6, pp. 255-268, 2009

Authors: Swellam, Menha | Sayed Mahmoud and, Magda | Abdel-Fatah Ali, Adel

Article Type: Research Article

Abstract: Objectives: To study the interrelationships of adiponectin, C-reactive protein (CRP) and fibrinogen with each other in T2DM patients with (T2DM-C) and without complications (T2DM-NC) among healthy individuals. Design and methods: The study comprised of 120 T2DM-C, 59 T2DM-NC patients and 40 healthy volunteers. Biochemical markers were determined in the serum. Results: Positivity rates of CRP and fibrinogen were significantly increased in T2DM-C as compared to T2DM-NC or controls, whereas adiponectin showed highest …level in healthy individuals. Inflammatory biomarkers were inversely correlated with adiponectin (P< 0.01). Lipid profiles, kidney functions and BMI, showed positive significant correlation with CRP and fibrinogen but negative correlation with adiponectin. For better detection of T2DM, the combined sensitivity (98.9%) and specificity (92.5%) of fibrinogen and adiponectin was higher than the combined sensitivity and specificity of fibrinogen and CRP or adiponectin and CRP or than that of the biomarkers alone. Conclusion: Elevated levels of CRP and fibrinogen and reduced level of adiponectin can be used for early diagnosis of T2DM and can predict diabetic complications. Show more

Keywords: Type 2 diabetes mellitus, adiponectin, c-reactive protein, fibrinogen

DOI: 10.3233/DMA-2009-0672

Citation: Disease Markers, vol. 27, no. 6, pp. 269-278, 2009

Authors: Kokotas, Haris | Grigoriadou, Maria | Mikkelsen, Margareta | Giannoulia-Karantana, Aglaia | Petersen, Michael B.

Article Type: Research Article

Abstract: Chromosomal aneuploidy consists the leading cause of fetal death in our species. Around 50% of spontaneous abortions until 15 weeks of gestational age are chromosomally aneuploid, with trisomies accounting for 50% of the abnormal abortions. Trisomy 21 is the most common chromosome abnormality in liveborns and is usually the result of nondisjunction of chromosome 21 in meiosis in either oogenesis or spermatogenesis. To investigate the relationship between folate metabolism and Down syndrome (DS) in a Danish …population, we analyzed the common 677C>T genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. Our cohort consisted of 181 mothers of children with DS versus 1,084 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to examine the MTHFR 677C>T polymorphism. No significant association between the polymorphism and the risk for DS was found. We conclude that the common MTHFR 677C>T polymorphism is not likely to be a maternal risk factor for DS in our cohort and that the difference to previous studies can probably be explained by small sample size or geographic variation in gene polymorphisms involving gene-nutritional or gene-gene or gene-nutritional-environmental factors. Show more

Keywords: Down syndrome, nondisjunction, MTHFR, polymorphism, risk factor

DOI: 10.3233/DMA-2009-0673

Citation: Disease Markers, vol. 27, no. 6, pp. 279-285, 2009

Authors: Shakoori, Tania Ahmed | Sin, Don D. | Ghafoor, Farkhanda | Bashir, Saira | Bokhari, S. Nazim Hussain

Article Type: Research Article

Abstract: Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. Objectives: To determine whether …or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. Study design: case control study. Methods: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n=13) and in control subjects (n=54) using a specific immunoassay and compared the levels using analysis of variance. Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL; p=0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV_{1} /FVC% predicted. Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations. Show more

Keywords: Surfactant protein D, serum biomarker, COPD, exacerbations, diagnostic

DOI: 10.3233/DMA-2009-0674

Citation: Disease Markers, vol. 27, no. 6, pp. 287-294, 2009

Authors: Maver, A. | Medica, I. | Salobir, B. | Tercelj, M. | Peterlin, B.

Article Type: Research Article

Abstract: Sarcoidosis is a systemic inflammatory disease characterised by appearance of granulomas. Precise etiology has not been elucidated. Osteopontin (Opn) is a Th1 cytokine whose levels have been found increased in granulomas and serum samples from patients with sarcoidosis. We investigated whether genetic variation in Osteopontin gene (OPN) gene contributes to susceptibility to sarcoidosis. Haplotype-block structure in the OPN gene region was investigated using data from HapMap project. Three representative SNPs have been selected …from each block of SNPs in linkage disequilibrium (rs11730582-C/T, rs11728697-C/T and rs4754-C/T). Genotyping was performed using TaqMan SNP Genotyping Assays on a sample of 165 patients and 284 controls. Statistical analyses of association were performed using Chi-Square test and algorithms implemented in the haplo.stats and PHASE packages. Genotyping analysis revealed a significant difference in genotype frequencies at rs4754 polymorphism in groups of patients and controls under recessive genetic model (p=0.036, OR=1.99, 95%CI=1.04–3.82), CC homozygotes being significantly over-represented in the patients group. However these results failed to reach significance after correction for multiple testing (p=0.25). The frequencies of predicted haplotypes differed between patient and control groups, frequency of TTT haplotype was found to be significantly decreased in the group of patients with sarcoidosis (p=0.014, OR=0.40, 95%CI=0.20–0.79). Our results suggest that variation in the OPN gene might be significantly associated with sarcoidosis and that the TTT haplotype in OPN may act as a protective factor in sarcoidosis. Show more

Keywords: Sarcoidosis, osteopontin, polymorphism, haplotype, association study

DOI: 10.3233/DMA-2009-0675

Citation: Disease Markers, vol. 27, no. 6, pp. 295-302, 2009

Authors: Ku, Bon-Jeong | Kim, Seul-Young | Lee, Tae-Yong | Park, Kang-Seo

Article Type: Research Article

Abstract: Background: The serum concentrations of ferritin and adiponectin are associated with several metabolic disorders and have been used as predictors of insulin resistance and metabolic syndrome. But there have been no reports demonstrating a direct correlation between serum ferritin and adiponectin levels. We performed this study to evaluate the association between serum ferritin and adiponectin concentrations. Subjects and methods: We evaluated a total of 995 subjects from the Korea Rural Genomic Cohort Study in …a population-based cross-sectional study. Extensive clinical and laboratory measurements, including adiponectin and ferritin concentrations, were recorded. Results: Univariate analysis revealed that the serum adiponectin level was correlated with age, sex, BMI, diastolic blood pressure, triglyceride, HDL-cholesterol, fasting blood glucose, fasting insulin, HOMA-IR, hs-CRP, and ferritin. Multivariate analysis demonstrated that the adiponectin concentration was correlated with age, BMI, fasting glucose, hs-CRP, and ferritin. The ferritin concentration was the most powerfully associated with serum adiponectin. In non-diabetic subgroups, the adiponectin level was correlated with BMI, triglyceride, HDL-cholesterol, fasting glucose, and ferritin level in multivariate analysis. In diabetic subgroups, the adiponectin level was correlated with BMI, triglyceride, hs-CRP, and ferritin level in multivariate analysis. Conclusions: The serum adiponectin concentration was correlated with conventional clinical variables, but the most powerfully associated factor was the serum ferritin level. Show more

Keywords: Adiponectin, ferritin, diabetes mellitus

DOI: 10.3233/DMA-2009-0676

Citation: Disease Markers, vol. 27, no. 6, pp. 303-310, 2009

Authors: De Chiara, Loretta | Rodríguez-Piñeiro, Ana M. | Cordero, Oscar J. | Rodríguez-Berrocal, Francisco J. | Ayude, Daniel | Rivas-Hervada and, Francisco J. | de la Cadena, María Páez

Article Type: Research Article

Abstract: Introduction: Previous studies have suggested the use of soluble CD26 (sCD26) as a tumour marker for the detection of colorectal cancer (CRC) and advanced adenomas. The aim of this study was to assess the sCD26 concentration in a large cohort to evaluate its association to epidemiologic parameters and CRC-related symptoms/pathologies. Subjects and methods: Serum samples were collected from 2,754 putatively healthy individuals with ages ranging from 30–65 years, and with personal or familial history …of polyps, CRC and/or CR symptoms. sCD26 levels were measured by ELISA. Results: No association was found between the sCD26 concentration and age (< 50 and ⩾ 50), the personal or familial history of polyps or CRC, rectal bleeding, haemorrhoids or diverticula. However, sCD26 was related to non-inflammatory benign pathologies (excluding rectal bleeding, changes in bowel habits, haemorrhoids, diverticula) and to inflammatory benign pathologies. Discussion: Our results confirm that the sCD26 can be easily offered and evaluated in a large cohort. Additionally, the validation of sCD26 as a tumour marker for screening and case-finding purposes requires a further comparison with an established non-invasive test like the faecal occult blood. Show more

Keywords: sCD26, serum levels, colorectal cancer, digestive pathologies, marker

DOI: 10.3233/DMA-2009-0679

Citation: Disease Markers, vol. 27, no. 6, pp. 311-316, 2009