Gul Ongen

Interleukin-10 and Tumor Necrosis Factor-α Gene Polymorphisms in Tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-α and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF- α. We analyzed TNF-α (−308 G/A, −238 G/A, −376 G/A) and IL10 (−1,082 G/A, −819 C/T, −592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and −1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45–3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45–3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35–0.81). No statistically significant association was found between IL-10 −819 C/T, TNF-α 308 G/A, −238 G/A, −376 G/A polymorphisms, functional TNFα/IL-10 genotypes and TB. Our findings suggest that IL-10 108 2G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis

Vitamin D receptor (VDR) gene variants may play a key role in the susceptibility to tuberculosis (TB). We have investigated the association BsmI, TaqI, FokI polymorphisms in the VDR gene with susceptibility to tuberculosis. This study included 128 patients with TB (pulmonary and extrapulmonary TB) and 80 healthy subjects living in Istanbul, Turkey. Genetic polymorphisms were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques at genomic DNA isolated from whole blood-EDTA. The present study results indicate that the genotype and allele frequencies for patient group (BB:22, Bb:53, bb:25; B allele:48%, b allele:52%) was significantly different from the control group (BB:6, Bb:48, bb: 46; B allele:30 b allele:70) due to an overrepresentation of B allele (P: 0.000 OR: 1.61 95% 1.23–2.11). However there were no significant differences in distribution of allele/genotype frequencies of FokI, TaqI variants between TB and healthy controls. This study results suggest that BsmI variant of VDR gene may play an important role in susceptibility to tuberculosis.

Extrapulmonary involvement in patients with sarcoidosis in Turkey

Background and objective:  Extrapulmonary sarcoidosis is common, and is almost always associated with concomitant thoracic involvement. Extrapulmonary manifestations vary on the basis of gender, age at presentation and ethnicity. The aim of this study was to investigate extrapulmonary involvement in patients with sarcoidosis in Turkey.

Factors Affecting the Tuberculosis Risk in Patients Receiving Anti-Tumor Necrosis Factor-α Treatment

Background: Tumor necrosis factor (TNF)-α inhibitors are known to increase the risk of tuberculosis (TB). Objectives: To examine the factors associated with an increased risk of TB in patients receiving anti-TNF-α treatment (aTNF-α-T). Method: Of 3,094 patients who received aTNF-α-T between 2003 and 2013, a total of 1,964 subjects with a follow-up time longer than 6 months were identified and included in this retrospective analysis. Potential risk factors for the development of TB in patients receiving aTNF-α-T were evaluated. Results: Of the 1,964 patients, 1,009 (51%) were male and 955 (49%) were female, with a mean age of 39.7 ± 13.9 years. The primary conditions requiring aTNF-α-T included ankylosing spondylitis (n = 875), rheumatoid arthritis (n = 711), Behçets disease (n = 83), and others (n = 295). Sixteen patients [8 (50%) males and 8 (50%) females; 5 (31.2%) with pulmonary TB and 11 (68.8%) with extrapulmonary TB] developed TB, with a corresponding TB incidence of 466/100,000. No significant associations were found between age, gender, smoking history, pack-years of smoking, isoniazid (INH) chemoprophylaxis, type of anti-TNF-α agent, use of other immunosuppressive drugs, and the risk of TB (p > 0.05). Multivariate logistic regression analysis showed a significantly higher risk of TB in patients diagnosed with Behçets disease, and a significantly lower risk of TB in patients with a tuberculin skin test wheal ≥10 mm in diameter (p < 0.05). Conclusion: aTNF-α-T is associated with an increased risk of pulmonary or extrapulmonary TB, even when follow-up protocols and INH chemoprophylaxis are implemented, and TB often develops in the later stages of treatment. The risk of TB was higher in patients with Behçets disease and lower in patients who had a strong tuberculin skin test reaction.

Association between 'interleukin' 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement.

Systemic sclerosis (SSc), also termed as “scleroderma”, is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Extracellular matrix (ECM) production by fibroblasts in SSc is modulated and regulated by cytokines. Since IL10 has antiinflamatory properties and, contributes to the fibrotic processes in SSc, we analyzed IL-10 gene polymorphisms including −1082 G/A, −819 C/T and −592C/A in 45 systemic sclerosis patients with lung involvement and 150 healthy control using ARMS-PCR. While no association was found between SSc and −819C/T, −592C/A polymorphism, −1082 G/A allele frequency in SSc patients was higher than that in control and significant association was found between SSc and −1082 G/A (Pc: <0.000, OR: 2.85 95% CI: 1.74–4.63). In addition significant difference was found between the frequencies of the IL-10 GCC, ACC haplotypes (Pc: <0.000, OR: 2.85, 95% CI: 1.74–4.63; Pc: 0.012, O.R: 1.56, 95% CI: 1.09–2.23, respectively), GCC+/GCC+, GCC−/GCC− genotypes (Pc: 0.002, OR: 5.07, 95% CI: 1.82–14.21; Pc: <0.000, O.R: 4.00, 95% CI: 1.87–8.98, respectively) and SSc. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may play role in SSc susceptibility.

NRAMP1 (SLC11A1): A Plausible Candidate Gene for Systemic Sclerosis (SSc) with Interstitial Lung Involvement

Systemic sclerosis (SSc), also termed “scleroderma,” is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor α, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5′ promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3′UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.

Sarcoidosis mimicking lymphoma on positron emission tomography-computed tomography in two patients treated for lymphoma: two case reports.

IntroductionSarcoidosis is a granulomatous disease that mostly involves the lungs. Its association with malignancies has been well documented. Several mechanisms have been proposed that may underlie this concurrence including triggering tumour antigens and defective cellular immunity.Case presentationsWe briefly review the literature on malignancy associated sarcoidosis and report two female lymphoma patients of 49 and 56 years of age who, during their course of disease, developed sarcoidosis that was misinterpreted as a lymphoma relapse on positron emission tomography-computed tomography.ConclusionWe hypothesise that T cell dysfunction and exposure to tumour associated antigens might be the underlying mechanisms of development of sarcoidosis in patients with lymphoma. Positron emission tomography-positive lesions do not always indicate malignancy and therefore a tissue biopsy is always mandatory to confirm the diagnosis.

The role of an activity monitor in the objective evaluation of patients with pulmonary hypertension

Patients with pulmonary hypertension (PH) show no symptoms at rest, but symptoms are triggered by physical activities.

Venous thromboembolism risk and thromboprophylaxis among hospitalized patients: data from the Turkish arm of the ENDORSE study.

Objectives: To evaluate venous thromboembolism (VTE) risk and use of thromboprophylaxis in the acute care hospital setting. Methods: A total of 1701 patients hospitalized for acute or exacerbated chronic medical illnesses or elective major surgery at 11 different hospitals across Turkey were included in the study. Patients at risk and VTE prophylaxis application were retrospectively identified based on medical charts. Results: According to the American College of Chest Physicians (ACCP) criteria, overall 35.6% (606 of 1701) of the patients were identified to be at VTE risk. Venous thromboembolism-risk was observed in 64.9% of surgical and 23.8% of medical patients, the latter being lower than global Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study results; while prophylaxis was prescribed in 39.0% and 38.5% of them, respectively. Contraindication to anticoagulant prophylaxis was observed in 8.7% of medical and 8.8% of surgical patients. Conclusions: VTE remains a risk factor among patients hospitalized across Turkey, since identification as well as prophylaxis of patients at VTE risk seems to be neglected.

Analysis of TNF polymorphisms in Turkish systemic sclerosis patients with interstitial lung involvement.

Systemic sclerosis (SSc), also termed scleroderma, is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities, and immune dysfunction (LeRoy et al. 1988). Clinical findings of scleroderma are sclerotic changes in the skin, joints, and internal organ systems, for instance, lungs, heart, and gastrointestinal tract (Haustein 2002; Medsger 1997). The major pathological process of scleroderma comprises inflammation (Brinckmann et al. 2005). Tumor necrosis factor (TNF), one of the cytokines involved in inflammation, is produced by monocytes (secrete TNF-a) and lymphocytes (secrete TNF-b and LTb) (Beutler and Cerami 1989). The TNF-a gene has a highly polymorphic transcriptional region (Li Kam Wa et al. 1999; Witte et al. 2002). The -308G/A