Disease Markers - Volume 33, issue 4

Authors: Morris, Charles P. | Baune, Bernhard T. | Domschke, Katharina | Arolt, Volker | Swagell, Christopher D. | Hughes, Ian P. | Lawford, Bruce R. | McD Young, Ross | Voisey, Joanne

Article Type: Research Article

Abstract: KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 …opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders. Show more

Keywords: KPNA3, genetic, schizophrenia, polymorphism, psychiatric disorder, cross-disorder

DOI: 10.3233/DMA-2012-0921

Citation: Disease Markers, vol. 33, no. 4, pp. 163-170, 2012

Authors: Zhu, Zhen-Long | Yan, Bao-Yong | Zhang, Yu | Yang, Yan-Hong | Wang, Zheng-Min | Zhang, Hong-Zhen | Wang, Ming-Wei | Zhang, Xiang-Hong | Sun, Xiao-Feng

Article Type: Research Article

Abstract: Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in …gastric adenocarcinoma. Patients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n=30) and gastric adenocarcinoma (n=73), from gastric cancer patients. Results: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X^{2} =9.711, p=0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X^{2} =11.151, p=0.001). PINCH expression was not correlated with patients' gender, age, tumour size, differentiation and invasion depth (p> 0.05). Comclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma. Show more

Keywords: PINCH, gastric adenocarcinoma, metastasis, immunohistochemistry

DOI: 10.3233/DMA-2012-0930

Citation: Disease Markers, vol. 33, no. 4, pp. 171-178, 2012

Authors: Anichini, C. | Lotti, F. | Longini, M. | Proietti, F. | Felici, C. | Perrone, S. | Buonocore, G.

Article Type: Research Article

Abstract: Oxidative stress (OS) is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS). Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals …takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced oxidation protein products (AOPP) and isoprostanes (IPs). Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex. Show more

Keywords: Prader Willi Syndrome, oxidative stress, potassium ascorbate with ribose, isoprostanes

DOI: 10.3233/DMA-2012-0922

Citation: Disease Markers, vol. 33, no. 4, pp. 179-183, 2012

Authors: Indulekha, K. | Surendar, J. | Anjana, R.M. | Gokulakrishnan, K. | Balasubramanyam, M. | Aravindhan, V. | Mohan, V.

Article Type: Research Article

Abstract: Aim: To look at the association of total and high molecular weight (HMW) adiponectin with markers of fat distribution, oxidative stress and inflammation in Asian Indians. Methods: A total of 120 subjects were chosen randomly from Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF-alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid peroxidation was measured by Tbars assay …and protein carbonyl content was assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by computed tomography (CT) scan. Results: When stratified based on the tertiles of visceral fat, the levels of total (p=0.03) and HMW adiponectin (p=0.007) were highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the levels of total (p=0.03) and HMW adiponectin decreased (p=0.002). The levels of HMW (p< 0.001) but not total adiponectin was also found to decrease with increasing tertiles of Protein carbonyl content. The levels of Total (p=0.02) and HMW adiponectin (p=0.004) were highest in the first tertile of oxidized LDL followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total (p=0.01) and HMW adiponectin (p=0.004) was found to decrease. With increasing tertiles of hs-CRP, Total (p=0.005) and HMWadiponectin (p=0.007)was found to decrease. Conclusion: Oxidative stress markers, visceral but not subcutaneous fat and inflammation are associated with total and HMW adiponectin levles in Asian Indians. Show more

Keywords: Metabolic syndrome, obesity, type 2 diabetes, Asian Indians, adipocytokines

DOI: 10.3233/DMA-2012-0924

Citation: Disease Markers, vol. 33, no. 4, pp. 185-192, 2012

Authors: Hong, Jun Hwa | Jang, Hye Won | Kang, Yea Eun | Lee, Ju Hee | Kim, Koon Soon | Kim, Hyun Jin | Park, Kyu Ri | Ku, Bon Jeong

Article Type: Research Article

Abstract: Background: The aim of this study was to investigate the role of the urinary chiro- and myo-inositol levels in predicting type 2 diabetes mellitus (T2DM). Subjects and methods: A total of 212 normal controls and 101 type 2 diabetic patients were enrolled this study. The concentrations of urinary chiro- and myo-inositol were measured by high performance liquid chromatography/mass spectrometry. Results: The concentration of urinary chiro-inositol was significantly higher in the diabetic subjects …(2.24 ± 5.18 ng/L) than those in the control group (0.38 ± 0.62 ng/L; p < 0.001). The urinary myo-inositol level of the diabetic subjects (36.95 ± 37.77 ng/L) was also significantly higher than that of the controls (8.17 ± 13.29 ng/L; p < 0.001). The urinary chiro-inositol multiplied by myo-inositol level of the diabetic subjects (148.10 ± 544.91) was significantly higher than in the controls (5.12 ± 24.15; p < 0.001). The area under the receiver operating characteristic curve for the urinary chiro-inositol multiplied by myo-inositol level to predict T2DM was 0.840 (confidence interval 0.789–0.891, p < 0.001). The cut-off value for the urinary chiro-inositol multiplied by myo-inositol level to predict T2DM was 2.20 (sensitivity 81.3%, specificity 70.3%). Conclusions: The urinary chiro- and myo-inositol concentrations were increased in the type 2 diabetic patients and the urinary chiro- times the myo-inositol was considered to be a sufficient marker in predicting T2DM. Show more

Keywords: Chiro-inositol, myo-inositol, diabetes mellitus

DOI: 10.3233/DMA-2012-0925

Citation: Disease Markers, vol. 33, no. 4, pp. 193-199, 2012

Authors: Ramírez-De los Santos, S. | Sánchez-Hernández, P.E. | Muñoz-Valle, J.F. | Palafox-Sánchez, C.A. | Rosales-Rivera, L.Y. | García-Iglesias, T. | Daneri-Navarro, A. | Ramírez-Dueñas, M.G.

Article Type: Research Article

Abstract: Objective: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28null T-cells, both present in synovial membrane of RA. Therefore we evaluated the associations of KIR genes with RA. Methods: 16 KIR genes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences in KIR genotypes and gene frequencies …were assessed using the X^{2} test. Results: Gene frequency of KIR2DL3 was lower in RA than in HS (p= 0.0019), whereas KIR2DL2 and KIR2DS2 were higher in RA than HS (p =0.0004 and p = 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p =0.0001, p =0.0208 and p =0.0300, respectively). Conclusions: The presence of KIR2DL2, KIR2DS2 and absence of KIR2DL3 are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest that KIRs can be involved in RA susceptibility. Show more

Keywords: KIR, killer cell immunoglobulin-like receptor, CD158, natural killer cell receptors, rheumatoid arthritis, autoimmune disease

DOI: 10.3233/DMA-2012-0927

Citation: Disease Markers, vol. 33, no. 4, pp. 201-206, 2012

Authors: Pradeep, AR | Priyanka, N | Prasad, MVR | Kalra, Nitish | Kumari, Minal

Article Type: Research Article

Abstract: Background: Obesity is considered as a strong risk factor of inflammatory periodontal tissue destruction. The purpose of this study is to determine presence of progranulin (PGRN) and high sensitivity C reactive protein (hs CRP) levels in serum and gingival crevicular fluid (GCF) in obese subjects with chronic periodontitis and to find an association, if any. Material and methods: 40 subjects (20 males and 20 females) were selected based on their clinical parameters into four groups (10 subjects in …each group): group 1 (healthy non obese), group 2 (healthy obese), group 3 (non obese with chronic periodontitis) and group 4 (obese with chronic periodontitis). Serum and GCF PGRN levels were estimated by enzyme linked immunosorbant assay (ELISA) and hs CRP levels were estimated by immunoturbidimetry method. Results: The mean PGRN and hs CRP concentration both in serum and GCF were highest for group 4 followed by group 3, group 2 and least in Group 1. Conclusion: PGRN and hs CRP may be novel biomarkers of the chronic inflammatory response in obesity and chronic periodontitis. Show more

Keywords: Chronic periodontitis, C reactive protein, progranulin, obesity

DOI: 10.3233/DMA-2012-0926

Citation: Disease Markers, vol. 33, no. 4, pp. 207-213, 2012

Authors: Samara, S. | Kollia, P. | Dailiana, Z. | Chassanidis, C. | Papatheodorou, L. | Koromila, T. | Malizos, K.N.

Article Type: Research Article

Abstract: Introduction: Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction. Lately, much focus has been at femoral head preservation with nonsurgical methods. In this study we examined the polymorphisms of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1β, IL-12, γIFN, TGF-β, TNF-a, IL-2, IL-4, IL-6 and IL-10 genes for evaluation of their contribution in ON. Material and methods: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis of the polymorphisms was completed …using the PCR-SSP method. Statistical analysis was performed using the χ ^{2} test to compare the genotype and allelic frequency distribution. Results: The CT and GA genotypes of the IL-1α (-889) and TNF-a (-238) genes were found higher in the patients (51.8% and 10.8%, respectively) compared to the healthy donors (39.7% and 2.1%, respectively). In TGF-β codon 25, the G to C polymorphism in the homozygous state was found in 1.8% of the patients and the C allele frequency was 8.9%, whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG genotype was 16.2% in the controls whereas in the patients was 7.2%. Conclusions: Based on the above, we showed that certain genotypes of the IL-1α, TGF-β, IL-10 and TNF-a genes could be related in the pathogenesis of a complicated disease, such as osteonecrosis. The presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may further increase the risk for osteonecrosis, especially in those at high risk, such as patients receiving corticosteroids. Show more

Keywords: Osteonecrosis, avascular necrosis, cytokines, interleukins, osteoblasts, osteoclasts

DOI: 10.3233/DMA-2012-0928

Citation: Disease Markers, vol. 33, no. 4, pp. 215-221, 2012