Betulinic acid may modulate autophagy in renal cell carcinoma cells.

OBJECTIVES: Betulinic acid is pentacyclic triterpenoid known to exert antitumor effects by modulating many cellular pathways in various human malignancies. However, its modulatory role in autophagy in renal cell carcinoma remains unclear. Here, we observed how betulinic acid affects autophagy in renal cell carcinoma cells. METHODS: After treating cells with betulinic acid, we determined the gene expression and protein levels of Beclin-1 and ATG-5 by qPCR and ELISA assay to observe its effects on autophagy. RESULTS: The qPCR results demonstrated that Beclin-1 expression level was low in untreated metastatic renal adenocarcinoma ACHN cells and increased in response to 25 µM and 50 µM betulinic acid treatment. ATG-5 expression level was decreased in primary clear cell renal cell carcinoma CAKI-2 cells treated with 50 µM betulinic acid. In the ELISA assay results, we observed that betulinic acid caused a decrease in Beclin-1 protein level at 25 µM concentration and in ATG-5 protein level at 50 µM concentration in CAKI-2 cells. CONCLUSION: In our preliminarily study, it was concluded that the role of autophagy may differ in renal cell carcinoma cells depending on their origin and that the effects of betulinic acid on autophagy in these cells may vary accordingly (Fig. 4, Ref. 40). Text in PDF www.elis.sk Keywords: betulinic acid, autophagy, kidney, cancer, cell.

Differential expression of miRNAs related to autophagy pathway in tissue and serum samples of colorectal cancer patients.

BACKGROUND: This study was aimed to investigate the relationship of miR-17-5p, miR-30b, miR-30d, miR-216a and miR-216b associated with autophagy gene beclin 1, and beclin 1 gene with colorectal cancer (CRC). MATERIALS AND METHODS: Forty-seven patients with CRC and 50 healthy individuals with no cancer history were included in this study. In the serum, tumor and non-tumoral tissue samples of the CRC patients, and in the serum samples of the healthy subjects, expression levels of miRNAs were detected by qRT-PCR. The beclin 1 gene expression levels were determined by qRT-PCR, and protein levels were determined by Western blot method in tumor and non-tumor tissue samples of the patients. RESULTS: The miR-17-5p and miR-30d expressions were found to be higher in tumor tissue as compared to patient non-tumor tissues, while expressions of beclin-1, miR-30b and miR-216a were found to be lower. In addition, the beclin-1 protein levels were significantly decreased in the tumor tissue as compared to those in the patient non-tumor tissues. The miR-30d expression was significantly reduced in the serum of the patients when the serum samples of CRC patients and healthy controls were compared. CONCLUSION: The beclin 1 gene may play a role as a tumor suppressor in CRC. Moreover, these miRNAs cannot be used as highly reliable biomarkers in serum for CRC diagnosis (Tab. 2, Fig. 6, Ref. 46).

Perspective of Turkish Medicine Students on Cancer, Cancer Treatments, Palliative Care, and Oncologists (ARES Study): a Study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

Cancer is one of the most common causes of death all over the World (Rahib et al. in Cancer Res 74(11):2913-2921, 2014; Silbermann et al. in Ann Oncol 23(Suppl 3):iii15-iii28, 2012). It is crucial to diagnose this disease early by effective screening methods and also it is very important to acknowledge the community on various aspects of this disease such as the treatment methods and palliative care. Not only the oncologists but every medical doctor should be educated well in dealing with cancer patients. Previous studies suggested various opinions on the level of oncology education in medical schools (Pavlidis et al. in Ann Oncol 16(5):840-841, 2005). In this study, the perspectives of medical students on cancer, its treatment, palliative care, and the oncologists were analyzed in relation to their educational status. A multicenter survey analysis was performed on a total of 4224 medical school students that accepted to enter this study in Turkey. After the questions about the demographical characteristics of the students, their perspectives on the definition, diagnosis, screening, and treatment methods of cancer and their way of understanding metastatic disease as well as palliative care were analyzed. The questionnaire includes questions with answers and a scoring system of Likert type 5 (absolutely disagree = 1, completely agree = 5). In the last part of the questionnaire, there were some words to detect what the words "cancer" and "oncologist" meant for the students. The participant students were analyzed in two study groups; "group 1" (n = 1.255) were phases I and II students that had never attended an oncology lesson, and "group 2" (n = 2.969) were phases III to VI students that had attended oncology lessons in the medical school. SPSS v17 was used for the database and statistical analyses. A value of p < 0.05 was noted as statistically significant. Group 1 defined cancer as a contagious disease (p = 0.00025), they believed that early diagnosis was never possible (p = 0.042), all people with a diagnosis of cancer would certainly die (p = 0.044), and chemotherapy was not successful in a metastatic disease (p = 0.003) as compared to group 2. The rate of the students that believed gastric cancer screening was a part of the national screening policy was significantly more in group 1 than in group 2 (p = 0.00014). Group 2 had a higher anxiety level for themselves or their family members to become a cancer patient. Most of the students in both groups defined medical oncologists as warriors (57% in group 1 and 40% in group 2; p = 0.097), and cancer was reminding them of "death" (54% in group 1 and 48% in group 2; p = 0.102). This study suggested that oncology education was useful for the students' understanding of cancer and related issues; however, the level of oncology education should be improved in medical schools in Turkey. This would be helpful for medical doctors to cope with many aspects of cancer as a major health care problem in this country.

Irak-4 rs4251481 gene variant: as a risk factor on inflammatory bowel disease

Background/aim: Abnormal immune response occurs in individuals who have alleles associated with innate and adaptive immune mechanisms that predispose to inflammatory bowel disease (IBD). Interleukin-1 receptor-associated kinase 4 (IRAK-4) involved in the pathway produces cytokines that initiate and maintain inflammation through Toll-like receptors and interleukin-1 receptors on the membranes of innate immune cells are stimulated with antigens. It was aimed to investigate whether IRAK-4 rs3794262 and rs4251481 polymorphisms predispose to IBD and the possible effects of these polymorphisms by examining these gene polymorphisms with the clinic and prognostic parameters of IBD. Materials and methods: Real-time PCR technique was used to detect IRAK-4 polymorphisms in 107 patients with IBD and 103 healthy controls. Results: As a result of experimental studies, the frequency of occurrence of rs4251481 polymorphism related AG genotype (P = 0.029) and G allele (P = 0.005) was found to increase statistically in patients compared to controls. In the control group, the rs4251481 AA genotype rate of incidence increased compared with the patient group (P = 0.005). Conclusion: Consequently, this is the first study in terms of both polymorphisms on IBD. These results suggest that rs4251481 AG genotype and G allele are associated with increased IBD risk in patients.

Serum sirtuin 1 protein as a potential biomarker for type 2 diabetes: Increased expression of sirtuin 1 and the correlation with microRNAs.

BACKGROUND: Type 2 diabetes (T2DM) is characterized by hyperglycemia and insulin deficiency. Sirtuin 1 (SIRT1), serving as a deacetylase, is critical in the regulation of glucose and lipid metabolism. Recently, a number of studies have been conducted to investigate the role of SIRT1 in the pathogenesis of T2DM. However, there are no sufficient data about the relationship between SIRT1 and T2DM. The aim of this study was to analyze the expressions of microRNAs (miRNAs) (miR-34a, miR-9, miR-132, and miR-181a) involved in SIRT1 regulation and SIRT1 protein in the serum of T2DM patients and controls. MATERIALS AND METHODS: miRNA expressions were determined by real-time polymerase chain reaction, and enzyme-linked immunosorbent assay was used to measure the SIRT1 protein levels in 25 T2DM patients and 25 controls. RESULTS: Fasting blood glucose and glycated hemoglobin levels were significantly higher in patients when compared with controls (P < 0.001). There was no difference for miRNA expressions between the groups (P > 0.05). SIRT1 protein level was significantly increased in patients as compared to controls (P = 0.044). Moreover, SIRT1 was negatively correlated with miR-181a (r = -0.558, P = 0.005) and miR-132 (r = -0.435, P = 0.034) in patients. CONCLUSION: Obtained results indicate that serum SIRT1 may be a potentially new biomarker for T2DM and also miR-181a and miR-132 may be involved in the development of T2DM by targeting SIRT1. This is the first study reporting on the effects of SIRT1 and related miRNAs in Turkish T2DM patients.

ROS related enzyme levels and its association to molecular signaling pathway in the development of head and neck cancer.

Given the prevalence and annual incidence of cancer, head and neck cancer is affecting more than 600,000 people each year. In this research, it was decided to investigate that which genes are involved and how MPO, NQO1, SOD2 enzyme levels effective to develop of head and neck cancer and for the first time at the tissue level. 35 tumor tissues in all head and neck anatomy and their surrounding tissue (70 in total) were enclosed the research that received surgery. Determination of the apoptosis genes expression levels (Mtch1, Akt1, Caspase3, Caspase9, Bcl2, Mdm2, mTOR) were determined by RT-PCR techniques and the same patients' sample used for ROS associated oxidant-antioxidant system by using MPO, NQO1, SOD2 enzyme levels using ELISA method. According to statistical results, caspase 9 gene was found statistically high expressed in early stage in contrast to late stage (p=0,013). Level of SOD2, NQO1 and MPO was determined and only MPO level was found significantly important on tumor tissues p=0,008).  Specially, our findings for high expression of Cas9 on early stage were thought to be the target for treatment with its well-known initiator role of the apoptosis. Our results suggest that the higher level of MPO in tumor tissues and indicates that it has some role on pathology of head and neck cancers. We believe that, our research will lead the proposal in-vivo studies and will open new areas on therapeutic targets.

Relation of MPO, MnSOD, NQO1 gene variants in endometrial carcinoma in the line of PCR-RFLP methods.

Reactive oxygen species (ROS) have been shown to be responsible for inducing DNA damage leading to mutagenesis, carcinogenesis, and cell death if the capacity of the protective antioxidant system is impaired. Endometrial carcinoma is the primary cancer type in the female genital system. The enhanced cell lipid peroxidation and impaired antioxidant enzyme activities observed in patients with endometrial cancer indicate the potential for oxidative injury to cells and cell membranes in such patients. The aim of the study was to investigate the possible association between gene variants of superoxide dismutase (SOD), myeloperoxidase (MPO), and NADPH quinone oxido reductase (NQO1), and their possible role in endometrial cancer in Turkish patients. According to results, MPO G+ genotype and AG genotype were significantly increased in patients compared with controls (P<0.001). We suggest that the MPO polymorphism might be a risk for endometrial cancer.

A Strong Relationship Between Oral Squamous Cell Carcinoma and DNA Repair Genes.

Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.

MMP-3 gene polymorphisms and Osteosarcoma.

Osteosarcoma (OSA) is the most common adolescence cancer among all primary bone tumors next only to multiplemyeloma. It has a substantially worse prognosis and ability to metastasize to lung. MMPs (matrix metalloproteinases) are among the major proteases that take part in regulation of ECM (extracellular matrix). MMPs play an active role in the formation of the osteoid tissue, rich in collagens and other ECM proteoglycans. They also take part in pro-osteoclast, osteoclast, osteoblast, and osteoid formation. Many members of the MMP gene family have been linked to human cancers. It has been shown that MMPs particularly play a role in the tumor's acquisition of an invasive and metastatic character. In our study, the E45K and T102T polymorphisms of MMP-3 were studied using the PCR-RFLP method in 135 Turkish subjects (54 subjects with osteosarcoma and 81 healthy controls). We found that frequencies of E45K G allele (p:0,010, χ²:6,710, OR:1,429, 95% Cl: 1,019-1,858) and AG genotype (p:0,001, χ²:14,753, OR:2,32, 95% Cl: 1,491-3,626) were elevated in patients compared to controls. Besides, there was a significant difference in.E45K AA genotype between study groups (p:0,004, χ²:8,182, OR: 2,929, 95% Cl: 1,38-6,19). There were no significant differences between any genotypes or allele in the control and patient groups for MMP-3 T102T polymorphism. Our findings indicate that the G allele and AG genotype of MMP-3 E45K polymorphism is associated with increased risk of osteosarcoma in adolescent population of Turkey.

Association between FAS and FASL genetic variants and risk of primary brain tumor.

The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012-0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007-0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.

Effects of micro environmental factors on natural killer activity (NK) of beta thalassemia major patients.

The physiological mechanisms of decreased NK activity of ß-Thalassemia major (BTM) patients are unknown. To assess in vitro effects of mononuclear cells and their cytokine secretion on NK activity, we compared activator receptor levels and cytotoxic activity of purified NK cells and NK cells in mononuclear cells (MNC) pools. We collected cell supernatant from unincubated and incubated MNC with K562 cells and measured their secreted cytokines levels. CD16 was lower on the surface of NK cells in MNC pools from BTM patients compared to healthy volunteers. This inhibition does not appear when NK cells were purified. NKp30 levels in NK cells decreased both as purified cells and as part of a pool of MNC in BTM patients. After incubation of MNC pools with K562 target cells, we found that supernatant levels of IL10, TGFß1 and IL15 cytokines were also significantly higher in BTM patients compared to healthy volunteers.

What if amoxicillin/clavulanic acid reduces the cisplatin anticancer impact on oral cancer treatment?

Antibiotics-chemotherapeutics combination have become on the table for many cancer treatments. For this reason, we thought that further progress and development of studies to support chemotherapeutic approaches with the use of antibiotics may be beneficial in the clinical field. Cell lines (SCC-15, HTB-41, and MRC-5) were treated with 5-100 µM/ml concentrations of cisplatin (cisp) and amoxicillin/clavulanic acid (amx/cla) with combination (amx/cla-cisp) and alone in three different incubation periods. The all-cells viability was examined with WST-1 and apoptotic activity of the drugs were investigated via cell death ELISA assay kit. The cytotoxic impact of the 100 µM amx/cla-cisp combination was found to be reduced by up to 21.8%, which was significant given that the cytotoxic effect of only cisplatin therapy was 86.1%. Because our findings demonstrated that solo amx/cla therapy have almost no impact on proliferation or death, we focused on the amx/cla-cisp combination effect. It was found that the amx/cla-cisp combination has reduced the apoptotic fragment when comparing with the solely cisp-treated cells. Due to amx/cla-cisp combination on both cells but significantly on SCC-15 recovered the sole cisplatin effect, we believe that there might be a second thought when prescribing antibiotics while treating cancer patients. Not only the antibiotic's type but also the cancer type might interact to lessen the chemotherapeutic agent's impact which is clinically a dilemma to focus on.

Kisspeptin-54 levels are increased in patients with colorectal cancer.

BACKGROUND: Recent studies have demonstrated that Kisspeptin, the product of the metastasis suppressor gene KiSS-1, could have a role in tumor progression and invasion. In this pilot study, we investigated the association of plasma Kisspeptin-54 level with colorectal cancer (CRC). METHODS: Plasma Kisspeptin-54 levels were quantified using enzyme-immunoassay (EIA) kits from blood samples of 81 patients with CRC at their initial staging and 59 age-matched healthy controls. RESULTS: Plasma Kisspeptin-54 levels were significantly higher in CRC patients (86.2 ± 20.5) than in controls (49 ± 12.7; p < 0.005). The cutoff value for Kisspeptin-54 detection was determined as 46 ng/ml, and area under curve (AUC) value was 0.766 with sensitivity 63 %, specificity 81.4 %, positive predictive value 82.2 %, negative predictive value 61.5 %, positive likelihood ratio 3.38, and negative likelihood ratio 0.46. Increased plasma Kisspeptin-54 levels were significantly correlated with nodal involvement of CRC (Spearman, rs = 0.345, p = 0.002). Kisspeptin-54 was also found to be an independent predictive marker for lymph node metastases of CRC (p = 0; Exp(B): 2.053; 95 % CI, 1.255-2.851). CONCLUSIONS: Our results reveal that plasma Kisspeptin-54 measurement could be a useful diagnostic and prognostic parameter for CRC. Further prospective evaluation is needed to validate these findings and to establish the clinical usefulness of Kisspeptin-54 for CRC diagnostics.

[Sinonasal extranodal natural killer/T-cell lymphoma: a case report and review of recent developments in the management]. / Sinonazal ekstranodal dogal katil/T-hücreli lenfoma: Olgu sunumu ve tedavideki son gelismelerin gözden geçirilmesi.

Nasal extranodal natural killer/T-cell lymphoma, which is a highly aggressive disease, is more frequently seen in Asia than in Western countries. No consensus has been reached on the management of the disease and the survival depends on the stage of the disease. Localized NK/T-cell lymphoma often responds to radiotherapy well. However, patients with advanced disease or recurrence after chemoradiotherapy, similar to our patient, have a very poor prognosis. In this article, we present a 52-year-old male patient with early recurrence and who was refractory to chemotherapy. The management of the disease was reviewed in the light of the recent literature data.

Effects of betulinic acid on AKT/mTOR pathway in renal cell carcinoma.

OBJECTIVE: Renal cancer is the most lethal among urological cancer. Treatments of renal cell carcinoma (RCC) may be possible by immune checkpoint inhibitors and drug treatment targeting different molecules. We aimed to determine the apoptotic effect of betulinic acid and its effects on expressions of apoptosisassociated genes AKT-1 and mTOR in RCC cells. MATERIAL AND METHODS: In this study, we investigated the apoptotic activity of betulinic acid in CAKI-2 cell line and its effect on AKT-1 and mTOR gene expression levels. In order to do so, following analyses were conducted: WST-1 to identify the toxic effect of betulinic acid, Caspase-3/BCA to detect caspase enzyme activity, Annexin-V and ELISA to determine for apoptotic effect, and finally, real-time PCR for expression levels of AKT-1 and mTOR. RESULTS: Our study showed that different concentrations of betulinic acid induced apoptosis in renal cancer; however, no effect was observed in healthy cells. In gene expression analysis, there was statistically significant decrease in AKT-1 expression level while increasing mTOR expression level. CONCLUSION: We suggested that betulinic acid with its apoptotic effect on RCC line and nontoxic effect on healthy cell line and the effects on AKT/mTOR pathway may be a potential anticancer drug promising for future studies.

The inhibitory effect of betulinic acid on epithelial-mesenchymal transition pathway in renal cell carcinoma.

Renal cancer is the most lethal urological cancer and characterized by high metastasis rate at initial diagnosis and drug resistance to current chemotherapeutics. Betulinic acid is a pentacyclic triterpene with broad biological activity that occurs naturally in variety of plants. Even though the anti-cancer efficacy of betulinic acid have been reported by many studies, the information about the pathways and the molecules which are affected by betulinic acid in renal cancer are limited. Epithelial-mesenchymal transition (EMT) is considered as the initial step of metastasis and contributes to drug resistance of cancer cells. Depending on the role of EMT in cancer progression and drug resistance, targeting EMT may represent an effective strategy in this context. Therefore, we aimed to investigate the anti-metastatic effects of betulinic acid on renal cell carcinoma cells by evaluating two EMT markers, SNAIL-1, and SDC-2. Following the treatment of betulinic acid at determined doses by WST-1 cytotoxicity assay in our previous study, SDC-2 expression level was decreased in both cell lines. Additionally, in correlation with this result, we also found a reduction in SDC-2 and SNAIL-1 protein levels which are measured by ELISA. Furthermore, the migration and invasion capacities were suppressed by betulinic acid treatment in metastatic renal adenocarcinoma ACHN cells. Taken together, our findings indicate that betulinic acid may constitute a potential treatment approach for renal cancer with further investigations.

The modulatory action of C-Vx substance on the immune system in COVID-19.

The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-α levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-γ and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1ß, IL-6, IL-8, IFN-γ and GM-CSF were significantly increased upon C-Vx stimulation. IFN-α levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.

Effects of myeloperoxidase -463 G/A gene polymorphism and plasma levels on coronary artery disease.

Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leucocytes that contributes to inflammatory responses. In previous studies it was shown that MPO was synthesized in atherosclerotic lesions responsible of lipoprotein oxidations. We aimed to determine the MPO -463 G/A gene polymorphism distribution in Turkish population and evaluate the effects of it on myeloperoxidase levels. There were 100 myocardial infarct patients and 100 healthy control subjects in our study. MPO polymorphism was studied by using PCR-RFLP technique and MPO levels were measured by ELISA. It was shown that MPO levels were increasing in patients after myocardial infarct event but there were no effect of MPO -463 G/A polymorphism on MPO levels. It was also found that serum total cholesterol and LDL-cholesterol levels and smoking was contributing factors in increments of MPO enzymes. We observed that MPO levels were increased in CAD but there were no effect of MPO -463 G/A polymorphism on MPO levels.

Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma.

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined by PCR-RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P=0.015). Besides, PON1 192 wild type QQ genotype (P=0.015) and PON1 55 wild type L allele (P=0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk of developing osteosarcoma.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch-Schönlein purpura.

AIM: Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch-Schönlein purpura (HSP). METHODS: Forty-one patients with HSP (25 male/16 female) with a mean age of 7.8 ± 2.9 years were included in the study. The control group consisted of 50 healthy children. MTHFR genotypes were determined by polymerase chain reaction and by Hindf I restriction enzyme analysis and subsequent 3% agarose gel electrophoresis techniques. RESULTS: No significant differences were observed in the distribution of MTHFR genotypes or allele frequencies in the HSP cases versus controls. Plasma homocysteine levels and vitamin B(12) levels were almost comparable in the HSP patients and control group without a significant difference. Folic acid levels were within normal limits in the HSP cases and the control group, HSP patients' levels being significantly higher than the control group. No significant relationship was present with the MTHFR genotype and plasma homocysteine, vitamin B(12) and folic acid levels in HSP patients. CONCLUSION: No association with MTHFR gene polymorphism and homocysteine plasma levels could be found in patients with HSP. The results of this study indicate that other mechanisms should be operative in the development of HSP.