Disease Markers - Volume 31, issue 1

Authors: Al Mutairi, Sana S. | Mojiminiyi, Olusegun A. | Shihab-Eldeen, Aida | Al Rammah, Tahani | Abdella, Nabila

Article Type: Research Article

Abstract: Aims: To investigate the hypothesis that circulating resistin reflects the degree of pulmonary inflammation, this study explores putative roles of resistin in patients with acute and stable inflammatory obstructive airway diseases and cigarette smokers. Methods: We determined complements C3, C4, fasting resistin, insulin, glucose and lipid profile; calculated insulin resistance (homeostasis model assessment (HOMA-IR) in patients with acute asthma exacerbation (n=34); stable asthma (n=26) and stable chronic obstructive pulmonary disease (COPD; n=26), cigarette smokers …(n=81), and healthy control subjects (n=42). We determined the associations between these variables and pulmonary function tests. Results: Patients with COPD, acute and stable asthma had significantly higher resistin and insulin than control subjects. Resistin, insulin, HOMA-IR, FEV1% and FEV1/FVC were significantly (p< 0.05) different between patients with acute asthma compared with stable asthma and COPD; smokers had similar levels of resistin, C3 and C4 as patients with asthma and COPD. In smokers, patients with asthma or COPD, resistin showed significant inverse correlations with FEV1%; FEV1/FVC% and positive significant correlations with BMI and HOMA-IR. Logistic regression showed that resistin is associated (p< 0.05) with inflammatory obstructive airways disease – odds ratio (OR)=1.22 and smoking OR=1.18. Conclusion: Resistin may be a disease activity marker and may contribute to insulin resistance in smokers, asthma and COPD. Show more

Keywords: Asthma, chronic obstructive pulmonary diseases, insulin resistance, resistin, smokers

DOI: 10.3233/DMA-2011-0793

Citation: Disease Markers, vol. 31, no. 1, pp. 1-7, 2011

Authors: Silva, G.E.B. | Costa, R.S. | Ravinal, R.C. | Ramalho, L.Z. | dos Reis, M.A. | Coimbra, T.M. | Dantas, M.

Article Type: Research Article

Abstract: Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB) in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1) to analyze the prognostic value of NF-kB expression in primary IgA nephropathy (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell tryptase and polyclonal …antibodies to TGF-β1, α-SMA and NF-kB p65. We used SWH for the in situ detection of activated NF-kB. The results showed that NF-kB expression (mainly by SWH) correlated with clinical and histological parameters. An unfavorable clinical course of IgAN was significantly related to tubular NF-kB expression by SWH, but not by IHC. The Kaplan-Meier curves demonstrated that increased NF-kB expression, which was measured by IHC and SWH, decreased renal survival. In conclusion, the increased expression of NF-kB in the tubular area may be a predictive factor for the poor prognosis of patients with IgAN. Compared with IHC, NF-kB expression determined by SWH was correlated with a larger number of parameters of poor disease outcome. Show more

Keywords: IgA nephropathy, southwestern histochemistry, NF-kB, renal fibrosis

DOI: 10.3233/DMA-2011-0795

Citation: Disease Markers, vol. 31, no. 1, pp. 9-15, 2011

Authors: Kim, Hyun Soo | Choi, Dongseok | Lim, Lyndell L. | Allada, Gopal | Smith, Justine R. | Austin, Carrie R. | Doyle, Trudy M. | Goodwin, Kelley A. | Rosenbaum, James T. | Martin, Tammy M.

Article Type: Research Article

Abstract: Interleukin 23 receptor (IL23R) gene has been reported as a genetic factor strongly associated with inflammatory bowel disease, psoriasis, and ankylosing spondylitis. We investigated the association between IL23R gene single nucleotide polymorphisms (SNPs) and susceptibility to sarcoidosis, including the clinical manifestation of uveitis. Ninety-one sarcoidosis subjects (58 with and 33 without uveitis) and 104 healthy controls were genotyped for eleven IL23R SNPs. DNA was amplified using specific PCR primers and …genotyped by denaturing HPLC and/or direct DNA sequencing. Case-control frequency comparisons were analyzed using Chi square test. Three IL23R SNPs, rs7517847 (intron 6), rs11465804 (intron 8), and rs11209026 (exon 9, c.1142G>A, p.Arg381Gln) were associated with sarcoidosis in our population (p<0.05): rs7517847 showed increased frequencies in sarcoidosis compared to controls, but rs11465804 and rs11209026 were decreased. Two of these SNPs were associated with the uveitis subgroup compared to controls: rs11465804 (0.9% vs. 7.2%, OR=0.11, P=0.013) and rs11209026 (1.8% vs. 7.3%, OR=0.23, P=0.038). This finding indicates the association of IL23R polymorphism with sarcoidosis, especially with sarcoid uveitis. IL23R may be a common susceptibility gene shared by several autoimmune disorders including inflammatory bowel disease, psoriasis, and ankylosing spondylitis and sarcoid uveitis. Show more

Keywords: Interleukin 23 receptor, polymorphism, sarcoidosis, uveitis

DOI: 10.3233/DMA-2011-0796

Citation: Disease Markers, vol. 31, no. 1, pp. 17-24, 2011

Authors: Balla, Bernadett | Pintér, Csaba | Kósa, János P. | Podani, János | Takács, István | Nagy, Zsolt | Speer, Gábor | Horváth, Balázs | Korányi, László | Lakatos, Péter

Article Type: Research Article

Abstract: Osteonecrosis of the femoral head (ONFH) is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using …multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone. Show more

Keywords: Osteonecrosis of femoral head, canonical variates analysis, human subjects, transcriptional profiling

DOI: 10.3233/DMA-2011-0797

Citation: Disease Markers, vol. 31, no. 1, pp. 25-32, 2011

Authors: Dalgic, Nazan | Tekin, Deniz | Kayaalti, Zeliha | Cakir, Erkan | Soylemezoglu, Tulin | Sancar, Mesut

Article Type: Research Article

Abstract: Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We …did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p> 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p=0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control. Show more

Keywords: Children, pulmonary tuberculosis, single nucleotide polymorphism, Toll-like receptor 8

DOI: 10.3233/DMA-2011-0800

Citation: Disease Markers, vol. 31, no. 1, pp. 33-38, 2011

Authors: Vikram, Naval K. | Bhatt, Surya Prakash | Bhushan, Bharat | Luthra, Kalpana | Misra, Anoop | Poddar, Pawan K. | Pandey, Ravindra M. | Guleria, Randeep

Article Type: Research Article

Abstract: Objectives: Obesity is associated with high levels proinflammatory cytokines like tumour necrosis factor alpha (TNF-α), which may play an important role in the genesis of insulin resistance. We evaluated the relationship of −308G/A polymorphism of TNF-α gene with obesity and insulin resistance in Asian Indians in north India. Methods: This cross-sectional study included 151 apparently healthy individuals (79 males, 72 females) 18–50 yrs of age from New Delhi, India. Body composition by dual-energy x-ray …absorptiometry (DEXA) and abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-α levels. We analysed −308G/A polymorphism of TNF-α gene and studied its association with obesity and biochemical parameters. Results: At comparable BMI, abdominal obesity was more prevalent in females (50%) as compared to males (20%). The wild genotype (GG) was present in 78.8%, GA in 17.9%, and AA in 3.3% subjects. Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP and TNF-α levels were not influenced by the presence of −308G/A polymorphism. Serum TNF-α levels correlated significantly with fasting insulin in both genders. Conclusion: TNF-α levels correlate with fasting insulin but not with indicators of body composition in Asian Indians. The −308G/A polymorphism of TNF-α gene is not associated with differences in the serum levels of TNF-α in Asian Indians. Show more

Keywords: TNF-α gene polymorphism, obesity, abdominal fat, insulin resistance, Asian Indians

DOI: 10.3233/DMA-2011-0802

Citation: Disease Markers, vol. 31, no. 1, pp. 39-46, 2011

Authors: Rasheed, Zafar | Al-Shobaili, Hani A. | Alzolibani, Abdullateef A. | Ismail Khan, Muhammad | Tariq Ayub, Muhammad | Khan, Mohammed Imran | Rasheed, Naila

Article Type: Research Article

Abstract: The role of oxidized immunoglobulin G in type 1 diabetic smokers has been investigated in the present study. Human immunoglobulin G (IgG) was modified by reactive oxygen species (ROS). The binding characteristics of circulating autoantibodies in type 1 diabetes patients against native and modified IgG were assessed by direct binding ELISA. High degree of specific binding by 68.5% of patients sera towards ROS-modified IgG was observed in comparison to its native analogue (p< 0.05). In addition, …diabetic smokers (n=28) were examined and the results were compared with diabetic non-smokers (n=26). Circulating antibodies of diabetic smokers showed substantially stronger binding to modified IgG as compared with the antibodies present in diabetic non-smokers (p< 0.05). Normal human sera (n=53) showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The increase in total serum protein carbonyl levels in the diabetic smokers was largely due to an increase in oxidized IgG. Diabetic smokers showed substantially higher carbonyl contents in sera as well as in purified IgG as compared with sera and IgG of diabetic non-smokers. Collectively, the oxidation of plasma proteins, especially IgG, might enhance oxidative stress in type 1 diabetes smokers. Show more

Keywords: Type 1 diabetic smokers, oxidized IgG, autoantibodies, reactive oxygen species

DOI: 10.3233/DMA-2011-0803

Citation: Disease Markers, vol. 31, no. 1, pp. 47-54, 2011