Disease Markers - Volume 32, issue 2

Authors: Zampieri, Bruna Lancia | Biselli, Joice Matos | Goloni-Bertollo, Eny Maria | Vannucchi, Hélio | Carvalho, Valdemir Melechco | Cordeiro, José Antônio | Pavarino, Érika Cristina

Article Type: Research Article

Abstract: Studies have shown that the maternal risk for Down syndrome (DS) may be modulated by alterations in folate metabolism. The aim of this study was to evaluate the influence of 12 genetic polymorphisms involved in folate metabolism on maternal risk for DS. In addition, we evaluated the impact of these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an indicator of vitamin B_{12} status) concentrations. The polymorphisms transcobalamin II (TCN2) c.776C>G, …betaine-homocysteine S-methyltransferase (BHMT) c.742A>G, methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) c.677 C>T and the MTHFR 677C-1298A-1317T haplotype modulate DS risk. The polymorphisms MTHFR c.677C>T and solute carrier family 19 (folate transporter), member 1 (SLC19A1) c.80 A>G modulate folate concentrations, whereas the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) c.66A>G polymorphism affects the MMA concentration. These results are consistent with the modulation of the maternal risk for DS by these polymorphisms. Show more

Keywords: Down syndrome, genetic polymorphism, folate metabolism

DOI: 10.3233/DMA-2011-0869

Citation: Disease Markers, vol. 32, no. 2, pp. 73-81, 2012

Authors: Yu, Wei | Hegarty, John P. | Berg, Arthur | Kelly, Ashley A. | Wang, Yunhua | Poritz, Lisa S. | Franke, Andre | Schreiber, Stefan | Koltun, Walter A. | Lin, Zhenwu

Article Type: Research Article

Abstract: PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly increased in intestinal tissues (p=0.0493), and nearly significantly increased in B cells (p=0.0889) from CD patients, but not significantly altered in UC. cDNA microarray results …found that PTPN2 was down-regulated by NKX2-3 knockdown in human cells. We confirmed this observation by RT-PCR analyses in NKX2-3 knockdown in B cells from IBD patients and human intestinal microvascular endothelial cells (HIMEC). In addition, we found that mRNA expression of another IBD-associated gene, NKX2-3, was increased in intestinal tissues and B cells from CD patients, but not significantly increased in UC patients. A positive correlation was observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal tissues from both CD and UC patients. These results suggest that PTPN2 may have an important role in CD pathogenesis and may represent a potential diagnostic and therapeutic target for IBD. Show more

Keywords: PTPN2, association, Crohn's disease, gene expression, NKX2-3

DOI: 10.3233/DMA-2011-0867

Citation: Disease Markers, vol. 32, no. 2, pp. 83-91, 2012

Authors: Cilenšek, Ines | Mankoč, Sara | Petrovič, Mojca Globočnik | Petrovič, Daniel

Article Type: Research Article

Abstract: Aim: Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy (DR). The aim of the present study was to investigate whether the genetic polymorphisms: polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 are associated with DR in Slovenian patients with type 2 diabetes. Methods: In this cross sectional case-control study 604 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients …with DR (cases) and the control group of 320 subjects with type 2 diabetes of more than 10 years' duration who had no clinical signs of DR. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: In our study, the deletion of the GSTM1 was found less frequent in cases with DR than in the controls (27.5% versus 44.4%; P < 0.001), whereas the deletion of GSTT1 was found significantly more often in cases than in the controls (49.3% versus 29.7%; P < 0.001). We did not find statistically significant differences in the genotype distribution in GSTP1 (Ile105Val) polymorphism between cases and controls (40.5% versus 46.0%). Conclusions: We may conclude that individuals homozygous for the deletion of GSTT1 are at an ≈ 2-fold-greater risk of DR, whereas the GSTM1 deficiency is associated with lower frequency of DR in type 2 diabetics. Show more

Keywords: Diabetes mellitus type 2, diabetic retinopathy, oxidative stress, glutathione S-transferase

DOI: 10.3233/DMA-2011-0863

Citation: Disease Markers, vol. 32, no. 2, pp. 93-99, 2012

Authors: Sharma, Anuj | Pradeep, A.R. | Raghavendra, N.M. | Arjun, P. | Kathariya, Rahul

Article Type: Research Article

Abstract: Cystatin C (CSTC) is an inhibitor of cysteine proteinases and could play a protective and regulatory role under inflammatory conditions. The present study was designed to assess the concentration of CSTC in gingival crevicular fluid (GCF) and serum, to find out their association if any, in periodontal health and disease. 30 subjects were selected divided into 3 groups consisting of 10 subjects in each group based on clinical parameters: periodontally healthy group, gingivitis group and chronic …periodontitis group, while, chronic periodontitis group after 8 weeks of the treatment (scaling and root planing) constituted after periodontal therapy group. GCF and serum samples were collected from all subjects to estimate the levels of CSTC by ELISA. The mean CSTC concentration in GCF and serum was observed to be the highest in periodontitis group and lowest in periodontally healthy group with intermediate concentration in gingivitis group and after periodontal therapy group. CSTC concentration in GCF and serum increased proportionally with the severity of periodontal disease (from health to periodontitis group) and decreased after treatment. This suggests that CSTC increases with disease progression to prevent further periodontal degeneration and decreases after treatment due to bone metabolic homeostasis. Further, longitudinal prospective studies involving larger population are needed to confirm the findings of present study and to better understand the role of CSTC in the pathogenesis of periodontal diseases. Show more

Keywords: Cystatin C, gingival crevicular fluid, serum, chronic periodontitis, gingivitis

DOI: 10.3233/DMA-2011-0864

Citation: Disease Markers, vol. 32, no. 2, pp. 101-107, 2012

Authors: Brambila-Tapia, Aniel Jessica Leticia | Durán-González, Jorge | Sandoval-Ramírez, Lucila | Mena, Juan Pablo | Salazar-Páramo, Mario | Gámez-Nava, Jorge Iván | González-López, Laura | Lazalde-Medina B, Brissia | Dávalos, Nory Omayra | Peralta-Leal, Valeria | del Mercado, Mónica Vázquez | Beltrán-Miranda, Claudia Patricia | Dávalos, Ingrid Patricia

Article Type: Research Article

Abstract: MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) …were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation. Show more

Keywords: MTHFR C677T, MTHFR A1298C, OPG A163G, polymorphisms, osteoporosis, rheumatoid arthritis

DOI: 10.3233/DMA-2011-0868

Citation: Disease Markers, vol. 32, no. 2, pp. 109-114, 2012

Authors: Sinthuwiwat, Thivaratana | Poowasanpetch, Phanasit | Wongngamrungroj, Angsana | Soonklang, Kamonwan | Promso, Somying | Auewarakul, Chirayu | Tocharoentanaphol, Chintana

Article Type: Research Article

Abstract: Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the …MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed. Show more

Keywords: MTHFR, aneuploidy, structural aberrations, polymorphism

DOI: 10.3233/DMA-2011-0862

Citation: Disease Markers, vol. 32, no. 2, pp. 115-121, 2012

Authors: Franko, Alenka | Dolzan, Vita | Kovac, Viljem | Arneric, Niko | Dodic-Fikfak, Metoda

Article Type: Research Article

Abstract: Soluble mesothelin-related peptides (SMRP) are a potential tumor marker for malignant mesothelioma. The aim of this study was to determine the differences in SMRP levels in patients with malignant mesothelioma before treatment and in various responses to treatment and to investigate whether SMRP level could be useful in evaluating tumor response to treatment. The study included patients with malignant mesothelioma treated at the Institute of Oncology Ljubljana between March 2007 and December 2009. Blood samples were …collected before treatment and/or in various responses to treatment. SMRP levels were determined using ELISA assay based upon a combination of two monoclonal antibodies. Mann-Whitney test was used to determine the differences in SMRP levels in various responses to treatment. Median SMRP was 2.80 nmol/L (range 0.00–34.80) before treatment, 0.00 nmol/L (range 0.00–0.00) in complete response, 0.48 nmol/L (range 0.00–4.40) in partial response, 1.65 nmol/L (range 0.00–20.71) in stable disease and 7.15 nmol/L (range 0.44–31.56) in progressive disease. Pre-treatment SMRP levels were significantly higher than in stable disease, partial response and complete response (p=0.006), as were SMRP levels in progressive disease compared to stable disease, partial response and complete response (p< 0.001). Our findings suggest that SMRP may be a useful tumor marker for detecting the progression of malignant mesothelioma and evaluating tumor response to treatment. Show more

Keywords: Malignant mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Tumor marker, Tumor response to treatment, Asbestos exposure

DOI: 10.3233/DMA-2011-0866

Citation: Disease Markers, vol. 32, no. 2, pp. 123-131, 2012

Authors: Hoyo, Cathrine | Murphy, Susan K. | Schildkraut, Joellen M. | Vidal, Adriana C. | Skaar, David | Millikan, Robert C. | Galanko, Joseph | Sandler, Robert S. | Jirtle, Randy | Keku, Temitope

Article Type: Research Article

Abstract: The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African …American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2. Show more

Keywords: IGF2R polymorphism, colon cancer, IGF2 concentration

DOI: 10.3233/DMA-2011-0865

Citation: Disease Markers, vol. 32, no. 2, pp. 133-141, 2012