Disease Markers - Volume 31, issue 4

Authors: Kalita, Jayantee | Somarajan, Bindu I. | Kumar, Bishwanath | Kumar, Sunil | Mittal, Balraj | Misra, Usha K.

Article Type: Research Article

Abstract: In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke. Consecutive patients with MRI proven ischemic stroke undergoing MRA were included in this study. The severity of atherosclerotic stenosis on MRA was categorized into moderate 50%–80%, severe 80%–99%, and total occlusion 100% using …NASCET criteria. The polymorphism in SNP 32, SNP 83 and SNP 87 of PDE4D gene was analyzed by PCR both in the patients and in 188 controls. Among the 148 patients, MRA was abnormal in 77% patients; ECMRA in 53.8%, ICMRA in 66% and both were abnormal in 42% patients. The frequency of CC genotype of PDE4D83 was significantly higher in the patients with ischemic stroke compared to controls (OR 3.38, 95% CI 1.61–7.11, P= 0.001). The frequency of TT genotype of PDE4D87 was significantly higher ICMRA abnormalities (20%) compared to normal ICMRA (2%). The genotype and allele frequency of PDE4D83 and PDE4D32 were not significantly related to MRA abnormalities. The role of PDE4D87 in atherosclerosis needs confirmation in larger studies. Show more

Keywords: Ischemic stroke, atherosclerosis, gene polymorphism

DOI: 10.3233/DMA-2011-0810

Citation: Disease Markers, vol. 31, no. 4, pp. 191-197, 2011

Authors: Rocha, Gustavo | Proença, Elisa | Areias, Augusta | Freitas, Fátima | Lima, Bruno | Rodrigues, Teresa | Alves, Helena | Guimarães, Hercília

Article Type: Research Article

Abstract: There is little data on the association between Human Leucocyte Antigen (HLA) alleles and Bronchopulmonary Dysplasia (BPD) of the preterm newborn. Our aim was to assess associations between HLA alleles and BPD susceptibility. We studied 156 preterm neonates (82 M/ 74 F) < 32 weeks gestational age, alive at 36 weeks gestational age. Detailed clinical data were collected. HLA typing was performed by PCR-SSO. HLA allele frequencies where determined by direct counting for BPD and no-BPD …groups. Comparison between BPD and no BPD groups was performed using t-test, χ2 test or Fisher exact test and logistic regression as appropriate. Relative risks (RR) and their 95% confidence intervals (95% CI) were also calculated as association measures. We diagnosed 56 (35.9%) neonates with mild BPD and 27 (17%) with moderate/ severe BPD. We found a significant association between HLA-DRB1*01 and mild BPD (OR=3.48[1.23–10.2]).The alleles HLA-A*24, -A*68, -B*51,-Cw*07, -Cw*14, -Cw*15 and -DRB1*01 presented a significant association with moderate/ severe BPD. When adjusted to gestational age and birth weight HLA-A*68 (OR=5.41[1.46; 20.05]), -B*51 (OR=3.09[1.11; 8.63]) and -Cw*14 (OR=4.94[1.15; 21.25]) were significantly associated with moderate/ severe BPD. Conclusion – Our findings suggest an association between HLA-A*68, -B*51 and -C*14 and BPD susceptibility, and that an autoimmune mechanism may be implicated in the pathogenesis of the disease. Show more

Keywords: HLA, major histocompatibility complex, bronchopulmonary dysplasia, preterm newborn

DOI: 10.3233/DMA-2011-0811

Citation: Disease Markers, vol. 31, no. 4, pp. 199-203, 2011

Authors: Yilmaz, Yusuf | Eren, Fatih | Yonal, Oya | Polat, Zulfikar | Bacha, Mohammad | Kurt, Ramazan | Ozturk, Oguzhan | Avsar, Erol

Article Type: Research Article

Abstract: Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and …sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Results: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t = 2.226, P < 0.01). Conclusions: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis. Show more

Keywords: Progranulin, nonalcoholic fatty liver disease, enzyme-linked immunosorbent assay, hepatic fibrosis

DOI: 10.3233/DMA-2011-0815

Citation: Disease Markers, vol. 31, no. 4, pp. 205-210, 2011

Authors: Tavakkoly-Bazzaz, Javad | Tabatabaei-Malazy, Ozra | Tajmir-Riahi, Mohammad | Javidi, Daryoosh | Izadi, Manizhe | Shahrabi-Farahani, Maryam | Amiri, Parvin | Amoli, Mahsa M.

Article Type: Research Article

Abstract: Objective: Klotho has an important role in development of coronary artery (CAD) disease. A functional variant of klotho gene (kl-vs) has been found as an independent risk factor for early-onset occult coronary artery disease (CAD) in previous studies. The Frequency of this variant was not known in Iranian population. We have examined the allele frequency of the kl-vs variant in a case-control study in an Iranian population. Methods and results: Genotyping for kl-vs variant was carried out in …N=107 individuals including N=54 cases and N=53 control who all underwent coronary angiogram for CAD evaluation. Patients with >50% stenosis in vessels considered as case groups (or CAD^{+} ) and patients with normal vessels (or CAD^{-} ) as controls. The frequency of kl-vs variant was determined in these patients using PCR-RFLP technique. None of the individual was carrying the kl-vs mutation in our samples. The frequency of kl-vs mutation was significantly different from previous studies in different populations. Conclusion: The kl-vs variant seems to be scare found in the Iranian population in comparison to other populations reported previously. Klotho gene might be a candidate gene of atherosclerosis in some populations but not in Iranian population. Further studies are required to examine the frequency of kl-vs variant in other populations from the Middle East. Show more

Keywords: Klotho gene, atherosclerosis, coronary artery disease

DOI: 10.3233/DMA-2011-0818

Citation: Disease Markers, vol. 31, no. 4, pp. 211-214, 2011

Authors: Saini, Vandana | Bhatnagar, M.K. | Bhattacharjee, Jayashree

Article Type: Research Article

Abstract: The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched …healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p< 0.001) whereas, the NO level in CAD group was significantly lower (p< 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p< 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population. Show more

Keywords: Nitric oxide, Coronary artery disease, Glu298Asp polymorphism, endothelin

DOI: 10.3233/DMA-2011-0819

Citation: Disease Markers, vol. 31, no. 4, pp. 215-222, 2011

Authors: Ota, Masao | Ito, Tetsuya | Umemura, Takeji | Katsuyama, Yoshihiko | Yoshizawa, Kaname | Hamano, Hideaki | Kawa, Shigeyuki

Article Type: Research Article

Abstract: Autoimmune pancreatitis (AIP), characterized by irregular narrowing of the main pancreatic duct, swelling of the pancreas, and histological evidence of lymphoplasmacytic inflammation by high serum immunoglobulin G4, is distinct from ordinary pancreatitis. However, genetic factors involved in the etiology and pathophysiology of AIP remain unclear. Sixty-four patients with autoimmune pancreatitis (53 men, 11 women; mean age, 62.4 years) and 104 healthy Japanese controls were enrolled in this study. We performed an association …analysis using 400 microsatellite markers with an average spacing of 10.8 cM in the genome. We also evaluated the association of AIP with seven single nucleotide polymorphisms (SNPs) within the 20-kb region around the potassium voltage-gated channel, shaker-related subfamily, member 3 gene (KCNA3). We identified six statistically significant markers (D1S2726, D5S410, D6S460, D10S548, D15S128, and D20S186; P< 0.05) related to susceptibility. The surrounding region showing the strong association (P=7.4 × 10^{-7} , Pc=0.0015) contained the KCNA3 gene. Further analysis by SNP genotyping in KCNA3 gene revealed that four SNPs (rs2840381, rs1058184, rs2640480, rs1319782) were significantly associated with the AIP susceptibility (P< 0.007). KCNA3 is known to be involved in immunomodulation of autoreactive effector and memory T cell--mediated autoimmune diseases. Our findings provide the first evidence that KCNA3 is associated with AIP and suggest that KCNA3 may influence the risk for AIP. Show more

Keywords: AIP, autoimmune pancreatitis, SNPs, KCNA3, disease susceptibility

DOI: 10.3233/DMA-2011-0820

Citation: Disease Markers, vol. 31, no. 4, pp. 223-229, 2011

Authors: Polimanti, Renato | Piacentini, Sara | De Angelis, Flavio | De Stefano, Gian Franco | Fuciarelli, Maria

Article Type: Research Article

Abstract: Over the last two decades, significant data has been accumulated linking Glutatione S-Transferases (GSTs) with the development of several diseases. Contemporary studies have demonstrated the impact of ethnicity on GST allele frequencies. The aim is to verify if the variability of GST genes reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian, n=77) and compared with HapMap data. …GST SNPs were determined using the PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR. The population relationship achieved using GSTM1 positive/null, GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data obtained using neutral polymorphisms: Amerindians are close to Asian populations and African-Ecuadorians to African populations. To what concerns GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%, showing no significant differences in the Ecuadorian groups and in worldwide populations. The features of GSTO1*del155 and GSTO1*K208 variants and their association with arsenic biotransformation deficiency suggest the presence of a selection mechanism towards these loci. In particular, this hypothesis is strengthened by a possible linkage between these alleles and the susceptibility of arsenic-induced male infertility. Show more

Keywords: Detoxification enzyme, Ecuador ethnic groups, natural selection, arsenic-induced male infertility

DOI: 10.3233/DMA-2011-0821

Citation: Disease Markers, vol. 31, no. 4, pp. 231-239, 2011

Authors: Pivovarova, Olga | Fisher, Eva | Dudziak, Katarzyna | Ilkavets, Iryna | Dooley, Steven | Slominsky, Petr | Limborska, Svetlana | Weickert, Martin O. | Spranger, Joachim | Fritsche, Andreas | Boeing, Heiner | Pfeiffer, Andreas F. H. | Rudovich, Natalia

Article Type: Research Article

Abstract: Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up-regulated in type 2 diabetes. In contrast, CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact of CTGF genetic …variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a common CTGF polymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association between CTGF polymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study (n=1026) (OR=0.637, CI (0.387–1.050); p=0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) (n=3049) cohort (RR=0.77 CI (0.49–1.20), p=0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family Study (n=1826). In conclusion, the polymorphism rs9493150 in the 5'-untranslated region of the CTGF gene has no association with T2DM risk and surrogate markers of beta-cell area. Show more

Keywords: Genetic association, connective tissue growth factor gene, C-peptide, blood glucose, beta-cell mass, type 2 diabetes mellitus

DOI: 10.3233/DMA-2011-0823

Citation: Disease Markers, vol. 31, no. 4, pp. 241-246, 2011