Disease Markers - Volume 28, issue 5

Authors: Arafa, Mohammad | Boniver, Jacques | Delvenne, Philippe

Article Type: Research Article

Abstract: Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers which may be relevant for the diagnosis, prediction of disease progression and therapeutic response. High throughput technologies for testing and validating molecular targets in cancer lesions and in their precursors are presently available. Among them, the tissue microarray (TMA) presents the advantage of a morphological control of …the analyzed tissue fragment. In this article, we review the different aspects of the TMA technology with a special consideration to a uterine carcinogenesis model. Show more

DOI: 10.3233/DMA-2010-0709

Citation: Disease Markers, vol. 28, no. 5, pp. 267-272, 2010

Authors: Lee, Silvia | Varano, Julius | Flexman, James P. | Cheng, Wendy | Watson, Mark W. | Rossi, Enrico | Adams, Leon A. | Bulsara, Max | Price, Patricia

Article Type: Research Article

Abstract: The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and …interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy. Show more

Keywords: Hepatitis C virus, interferon-based therapy, chemokines, fibrosis

DOI: 10.3233/DMA-2010-0699

Citation: Disease Markers, vol. 28, no. 5, pp. 273-280, 2010

Authors: Das, Swapan K. | Sharma, Neeraj K. | Elbein, Steven C.

Article Type: Research Article

Abstract: Recent studies in mice and human identified osteocalcin (OCN) as a bone-derived hormone that modulates insulin secretion and insulin sensitivity. OCN is synthesized by the bone gamma-carboxyglutamate protein (BGLAP) gene located in the well replicated region of type 2 diabetes (T2D) linkage on chromosome 1q22. We resequenced BGLAP gene in 192 individuals with T2D and performed case-control studies in 766 Caucasian (461 T2D and 305 controls) and 563 African American individuals (371 T2D and 192 controls). …Metabolic effects of BGLAP variants were examined in 127 nondiabetic members of Caucasian T2D families and in 498 unrelated nondiabetic African American and Caucasian individuals. BGLAP expression was tested in transformed lymphocytes from 60 Caucasian individuals. We identified 17 single nucleotide polymorphisms (SNPs) in African Americans, but observed only the two known SNPs in Caucasians. No SNP was associated with T2D. Promoter SNP rs1800247 was not associated with metabolic traits including insulin sensitivity (S_{I} ) or fasting glucose in either population, but nonsynonymous SNP rs34702397 (R94Q) was nominally associated with S_{I} (uncorrected p=0.05) and glucose-mediated glucose disposal (S_{G} ; uncorrected p=0.03) in African Americans. No SNP altered measures of insulin secretion or obesity, nor was BGLAP expression associated with rs1800247. Our study was sufficiently powered to exclude BGLAP variants as a major risk factor (OR > 1.5) for T2D in Caucasians, but coding variants in exon 4 may alter glucose homeostasis and diabetes risk in African Americans. Show more

Keywords: Osteocalcin, diabetes, polymorphism, transcript, association, insulin sensitivity

DOI: 10.3233/DMA-2010-0701

Citation: Disease Markers, vol. 28, no. 5, pp. 281-286, 2010

Authors: Guida, Valentina | Lepri, Francesca | Vijzelaar, Raymon | De Zorzi, Andrea | Versacci, Paolo | Digilio, Maria Cristina | Marino, Bruno | De Luca, Alessandro | Dallapiccola, Bruno

Article Type: Research Article

Abstract: GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs), mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number …variations (CNVs) in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA) a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis. Show more

Keywords: CHD, MLPA, GATA4, CNV

DOI: 10.3233/DMA-2010-0703

Citation: Disease Markers, vol. 28, no. 5, pp. 287-292, 2010

Authors: Vraneković, Jadranka | Babić Božović, Ivana | Starčević Čizmarević, Nada | Buretić-Tomljanović, Alena | Ristić, Smiljana | Petrović, Oleg | Kapović, Miljenko | Brajenović-Milić, Bojana

Article Type: Research Article

Abstract: Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two common MTHFR polymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence of MTHFR C677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a …liveborn DS child (n=102) or DS pregnancy (n=9) and mothers with a healthy child (n=141). MTHFR C677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using χ ^{2} test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of the MTHFR C677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility that MTHFR polymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population. Show more

Keywords: Down syndrome, enzyme configuration, MTHFR, polymorphisms

DOI: 10.3233/DMA-2010-0704

Citation: Disease Markers, vol. 28, no. 5, pp. 293-298, 2010

Authors: Swellam, Menha | Mahmoud, Magda Sayed | Samy, Nervana | Gamal, Ali Ahmed

Article Type: Research Article

Abstract: Objectives: Genes encoding for cytokines have been associated with susceptibility for joint osteoarthritis (OA) and interleukin (IL)-1 gene is supposed to be involved in the cartilage destruction process. In this regard, interleukin-1 receptor antagonist (IL-1RA) competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. We assessed the association of primary knee OA with IL-1RA region as a putative factor of susceptibility to knee OA in Egyptian patients. …Design and methods: Eighty patients with primary knee OA and 40 aged-matched healthy controls were included into the study. DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction (PCR) in both groups. Results: An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was found in OA patients relative to controls (60.5% vs. 39.5%, P=0.039, 85.4% vs. 14.6%, P=0.002, respectively) however, only the carriage rate of IL-1RN*2 allele was found to be significant when OA patients were compared to the controls. Significant higher frequencies of IL-1RN*1/*2 and IL-1RN*2/*2 genotypes in OA patients were observed as compared with controls. Both visual analogue scale (VAS) {and radiographic score revealed} significant correlation with both the allelic frequency and the carriage rate of IL-1RN*2 allele. Moreover, absolute frequency of IL-1RN*1/*2 genotype OA patients revealed severe VAS and high radiographic score. Conclusion: These results suggest that IL-1RN*2 allele represent a significant factor influencing the severity and course of knee OA; thereby supporting the potential role of IL-1 in the pathogenesis of this disease. Show more

Keywords: Knee osteoarthritis, interlukin-1, interleukin-1 receptor antagonist

DOI: 10.3233/DMA-2010-0708

Citation: Disease Markers, vol. 28, no. 5, pp. 299-305, 2010

Authors: Srivastava, Anshika | Garg, Naveen | Srivastava, Anvesha | Srivastava, Kshitij | Mittal, Balraj

Article Type: Research Article

Abstract: Background: ATP-binding cassette transporter ABCG8 plays an important role in excretion of cholesterol from liver. Common genetic polymorphisms in ABCG8 gene may genetically predispose an individual to coronary artery disease (CAD) along with response to atorvastatin therapy. Thus, we aimed to examine the role of ABCG8 D19H polymorphism (rs11887534) in susceptibility to CAD and its influence on atorvastatin response. Methodology: The study included 213 CAD patients and 220 controls. Genotyping of ABCG8 D19H polymorphism …was done by PCR-RFLP. Results} Our results showed that ABCG8 'H' allele was conferring significant risk for CAD in a dominant model (OR=2.54; p=0.014). This increased risk for CAD was more pronounced in males (OR=2.69; p=0.030). No correlation of ABCG8 genotypes with the risk factors (diabetes, hypertension and smoking) of CAD was observed. On atorvastatin treatment there was a significant decrease in the LDL-C levels (p=0.021). However, stepwise multiple regression analysis showed that this decease was not associated with ABCG8 genetic variant (p=0.845). Observed determinants of variation in interindividual response to atorvastatin therapy were pre-treatment LDL-C (p= 0.024) and TC (p=0.017). Conclusion: Although the genetic variant 19H of ABCG8 confers risk for CAD in North Indian population, it is not associated with interindividual response to atorvastatin therapy. Show more

Keywords: Coronary artery disease, polymorphism, ABCG8, Atorvastatin therapy, PCR-RFLP

DOI: 10.3233/DMA-2010-0710

Citation: Disease Markers, vol. 28, no. 5, pp. 307-313, 2010

Authors: Choi, Ihn-Geun | Woo, Sung-Il | Kim, Ho Jin | Kim, Dai-Jin | Park, Byung Lae | Cheong, Hyun Sub | Pasaje, Charisse Flerida A. | Park, Tae Joon | Bae, Joon Seol | Chai, Young Gyu | Shin, Hyoung Doo

Article Type: Research Article

Abstract: The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association of PRNP*129Val with multiple sclerosis (MS, n=681), mild cognitive impairment (MCI, n=801), alcoholism (n=761) and schizophrenia (n=715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency of PRNP*129Val (MAF …=0.025) was significantly lower in Korean population (n=2,479) compared to Caucasian populations (P < 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association between PRNP*129Val and MS (P= 0.76), MCI (P=0.46), alcoholism (P=0.84) and schizophrenia (P =0.69). These findings were discussed in the context of prior inconsistent reports on the role of PRNP*129Val polymorphism in several diseases. Results from this study may provide further evidence that PRNP M129V is not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population. Show more

Keywords: Prion, PRNP M129V, multiple sclerosis, mild cognitive impairment, alcoholism, schizophrenia

DOI: 10.3233/DMA-2010-0711

Citation: Disease Markers, vol. 28, no. 5, pp. 315-321, 2010

Authors: Juárez-Velázquez, Rocio | Canto, Patricia | Canto-Cetina, Thelma | Rangel-Villalobos, Hector | Rosas-Vargas, Haydee | Rodríguez, Maricela | Canizales-Quinteros, Samuel | Velázquez Wong, Ana Claudia | Ordoñez-Razo, Rosa María | Vilchis-Dorantes, Guadalupe | Coral-Vázquez, Ramón Mauricio

Article Type: Research Article

Abstract: Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1)} polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ^2 tests. …All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. Show more

Keywords: Gene polymorphisms, AGT, GPIIIa, GSTP1, MTHFR, Mexican populations

DOI: 10.3233/DMA-2010-0712

Citation: Disease Markers, vol. 28, no. 5, pp. 323-331, 2010