Disease Markers - Volume 27, issue 1

Authors: Rodríguez-Pérez, Noelia | Aguinaga-Barrilero, Ana | Gorroño-Echebarría, Marina B. | Pérez-Blas, Mercedes | Martín-Villa, José M.

Article Type: Research Article

Abstract: Uveitis is a clinical feature of the Blau syndrome, a disease linked to CARD15 (also referred to as NOD2) mutations. Three main mutations in this gene (R334W, R334Q and L469F) have been reported as Blau syndrome risk factors, a disease that manifests uveitis as one of its clinical features. However, little is known on the involvement of this gene in idiopathic uveitis. We thus sought to determine the frequency of these Blau-related CARD15 mutations in a …cohort of Spanish patients with idiopathic uveitis. To this aim, 110 patients with idiopathic uveitis, followed at the Department of Ophtalmology of a tertiary hospital (Hospital Universitario Alcalá de Henares, Madrid. Spain) were enrolled. As a control population, 104 healthy subjects were used. DNA was extracted from blood samples and the Blau-related CARD15 mutations were analysed either by PCR-RFLP or direct DNA sequencing. None of the mutations studied was found in any of the individuals tested, whether diseased or healthy. It seems thus that Blau syndrome-related CARD15 mutations are not involved in idiopathic uveitis, a finding which allows us to suggest that the genetic aetiology of the idiopathic uveitis or the Blau-associated uveitis is different. Show more

Keywords: Blau syndrome, CARD15, idiopathic uveitis, NOD2

DOI: 10.3233/DMA-2009-0639

Citation: Disease Markers, vol. 27, no. 1, pp. 1-5, 2009

Authors: Badadani, Mallikarjun | Babu, S.V. Suresh | Shetty, K.T. | Agarwal, S.S.

Article Type: Research Article

Abstract: Handigodu Disease (HD) is disorder of the osteoarticular system prevalent in few villages of two districts of the state Karnataka in southern India. 24 hrs urinary excretions of proline (Pro) and 4-hydroxyproline (Hyp) were analyzed by HPLC. Decreased peptide bound Hyp excretions (μmole/24 hrs) were found in patient group when compared with controls (Nonaffected; 113.02 ± 67.96, Type-I; 36.22 ± 20.76, Type-II; 45.74 ± 14.95, Type-III; 40.46 ± 22.68) and without significant …difference in Pro excretions. Significant increased peptide bound Pro to Hyp ratio were found in patient group compared to control (Nonaffected n=63: 2.02 ± 1.65, Type-I n=18: 3.144 ± 1.42, Type-II n=28: 4.21 ± 1.95, Type-III n=8: 8.60 ± 6.55). 24 hrs urinary excretions of deoxypyridinoline (DPD) crosslinks were found without significant difference among affected and control, hence HD ruled out from general bone reduction. These results suggest hypohydroxyprolinuria may be because of reduced bone turnover or defective hydroxylation of prolyl residues during post translational modification of collagen biosynthesis. Show more

Keywords: Handigodu disease, peptide bound, hypohydroxyprolinuria, dinitrophenyl

DOI: 10.3233/DMA-2009-0640

Citation: Disease Markers, vol. 27, no. 1, pp. 7-12, 2009

Authors: Santos-Rebouças, Cíntia Barros | Abdalla, Cláudia Bueno | Martins, Paloma Águia | Baldi, Fábio José Rodrigues | Santos, Jussara Mendonça | Motta, Luciana Branco | de Borges, Margarete Borges | Souza, Dorotéia Rossi Silva | de Souza Pinhel, Marcela Augusta | Laks, Jerson | Pimentel, Márcia Mattos Gonçalves

Article Type: Research Article

Abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have emerged as a potential common cause for both sporadic and familial Parkinson's Disease (PD) in different populations. The pleomorphic features exhibited by LRRK2 mutation carriers and the central role of Lrrk2 protein in the proper functioning of central nervous system suggest that mutations in this protein might be involved in multiple cellular processes leading to other neurodegenerative disorders than PD. The location of …LRRK2 gene on chromosome 12, close to a linkage peak for familial late-onset Alzheimer's Disease (AD), highlights that LRRK2 mutations might be involved in AD pathogenesis. We screened the most common LRRK2 mutation (p.G2019S) in a series of 180 consecutive patients clinically diagnosed with Alzheimer Disease (AD). We identified the p.G2019S in one AD patient with no PD signs, indicating that this mutation is not a common etiological factor for AD in our population (0.5%), corroborating recent data found in Norwegian, North American, Chinese and Italian populations. Nevertheless, these observations together with new information about the Lrrk2 critical multifunctionality do not rule out the possible influence of other variants within LRRK2 in AD, so that other screenings focusing in the whole extension of the LRRK2 using larger sized confirmed AD sample are urgently needed. Show more

Keywords: Alzheimer's disease, Leucine-rich repeat kinase 2, LRRK2, p.G2019S mutation, Parkinson's disease

DOI: 10.3233/DMA-2009-0641

Citation: Disease Markers, vol. 27, no. 1, pp. 13-16, 2009

Authors: Alkhateeb, Asem | Uzrail, Amal | Bodoor, Khaldon

Article Type: Research Article

Abstract: Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron …overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes) from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR) to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP) method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases) and controls (blood donors, 204 cases) and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting finding of no C282Y allele detected in 440 samples. Additionally, no significant difference was observed in H63D variant frequency in type 2 diabetics as compared to controls. Show more

Keywords: Hemochromatosis, HFE, diabetes, H63D

DOI: 10.3233/DMA-2009-0642

Citation: Disease Markers, vol. 27, no. 1, pp. 17-22, 2009

Authors: Lin, Yingsong | Nakachi, Kei | Ito, Yoshinori | Kikuchi, Shogo | Tamakoshi, Akiko | Yagyu, Kiyoko | Watanabe, Yoshiyuki | Inaba, Yutaka | Kazuo Tajima for the JACC Study Group,

Article Type: Research Article

Abstract: Elevated serum or plasma Transforming Growth Factor-β1 (TGF-β1) {levels have been} linked to cancer and other diseases in numerous studies; however, very few studies have reported an association between circulating TGF-β1 and lifestyle factors in healthy people. We examined the association between serum TGF-β1 levels and gender, age, body mass index (BMI), smoking, and drinking in a large population-based cohort study (N =9,142). Serum TGF-β1 levels were {detected by the Quantikine enzyme-linked …immunoassay kit (R&D Systems). The data indicated highly significant (p< ;0.0001) difference in serum TGF-β1 levels between men (mean value: 37.6 ± 0.12 ng/mL, N=4888) and women (mean value: 35.1 ± 0.12 ng/ml, N=4254).} Serum TGF-β1 levels decreased with age (trend p< 0.0001) and were positively associated with obesity (trend p< 0.0001) in both men and women. We observed a significant trend with increased serum TGF-β1 levels corresponding to increased amount of tobacco and alcohol consumption in men (trend p< 0.0001). These findings suggest that serum TGF-β1 levels appear to be modulated by {gender}, age and lifestyle factors such as obesity, cigarette smoking, and alcohol drinking in healthy Japanese adults. Show more

Keywords: Serum TGF-β1, gender, age, smoking, obesity

DOI: 10.3233/DMA-2009-0643

Citation: Disease Markers, vol. 27, no. 1, pp. 23-28, 2009

Authors: Stefanidis, Ioannis | Kytoudis, Kyriakos | Papathanasiou, Afroditi A. | Zaragotas, Dimitrios | Melistas, Lambros | Kitsios, Georgios D. | Yiannakouris, Nikolaos | Zintzaras, Elias

Article Type: Research Article

Abstract: Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1) contributes to development of microangiopathy in diabetes mellitus type 2 (DM) patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN). Study population (n=240) consisted of 148 unrelated patients with DM …(92 cases with diabetic nephropathy (DN)), and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (>300 mg/24 h) and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(−) carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR) 2.08 [95% confidence interval (1.14–3.79)]. However, there was no evidence of association between XbaI(−) and DN when patients with DM and without DN were considered as controls: OR=1.12 (0.55–2.26). Thus, the GLUT1 XbaI(−) allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN. Show more

Keywords: Diabetes type 2, diabetic microangiopathy, diabetic nephropathy, GLUT1, polymorphism

DOI: 10.3233/DMA-2009-0648

Citation: Disease Markers, vol. 27, no. 1, pp. 29-35, 2009

Authors: Puchau, Blanca | Hermsdorff, Helen Hermana M. | Zulet, M. Ángeles | Martínez, J. Alfredo

Article Type: Research Article

Abstract: The purpose of this study was to evaluate whether the mRNA expression profiles of three genes (PRMT1, DDAH2 and NOS3) are related to ADMA metabolism and signalling, and the potential relationships with anthropometrical, biochemical, lifestyle and inflammatory indicators in healthy young adults. An emphasis on the putative effect of different mRNA expression on cardiovascular risk-related features was paid. Anthropometrical measurements as well as lifestyle features were analyzed in 120 healthy young adults. …Fasting blood samples were collected for the measurement of glucose and lipid profiles as well as the concentrations of selected inflammatory markers. Profiles of mRNA expression were assessed for PRMT1, DDAH2 and NOS3 genes from peripheral blood mononuclear cells. Regarding inflammatory biomarkers, DDAH2 was inversely associated with IL-6 and TNF-α. Moreover, subjects in the highest quintile of DDAH2 mRNA expression showed a reduced risk to have higher values of waist circumference, and to be more prone to show higher values of HDL-c. Interestingly, DDAH2 gene expression seemed to be related with some anthropometrical, biochemical, lifestyle and inflammatory indicators linked to cardiovascular risk in apparently healthy young adults, emerging as a potential disease marker. Show more

Keywords: Protein arginine N-methyltransferase type I 1 (PRMT1), dimethylarginine dimethylaminohydrolase 2 (DDAH2), nitric oxide synthase 3 (NOS3), cardiovascular risk, asymmetric dimethylarginine (ADMA), atherosclerosis

DOI: 10.3233/DMA-2009-0650

Citation: Disease Markers, vol. 27, no. 1, pp. 37-44, 2009