Lack of association of the M129V polymorphism of the PRNP gene with pseudoexfoliation syndrome

Marios P Giannakopoulos,1 Anna G Antonacopoulou,2 Anastasia E Kottorou,2 Haralabos P Kalofonos,2 Sotirios P Gartaganis1 1Department of Ophthalmology, School of Medicine, 2Department of Medicine, Molecular Oncology Laboratory, Division of Oncology, University of Patras, Rion, Greece Purpose: In this study we aimed to evaluate the polymorphism at codon 129 (M129V) of the PRNP gene as a secondary risk factor for pseudoexfoliation syndrome (PEX). Methods: Two hundred and seventy-five unrelated subjects, including 156 patients with PEX and 119 unrelated control subjects, were recruited from the University Hospital of Patras, Greece. All patients and controls were of Caucasian or European ancestry. The PRNP M129V (A/G) single-nucleotide polymorphism was genotyped by real-time polymerase chain reactions. Association of the polymorphism with PEX was assessed using the two-sided Pearson’s chi-squared or Fisher’s exact test.Result: No significant difference between patients and controls was observed in terms of frequencies of alleles and genotypes of the PRNP gene.Conclusion: Polymorphism at M129V of the PRNP gene was evaluated as a secondary risk factor for developing PEX. Our results suggest that this PRNP gene polymorphism is not associated with PEX. Keywords: pseudoexfoliation syndrome, polymorphism, M129V, PEX, protein folding disorder

VEGF

Aims: Colorectal cancer (CRC) is the third most common cancer in the world and its etiology involves the interaction of genetic and environmental factors. New blood vessels form through a process called angiogenesis and have an essential role in tumor growth, progression, and metastasis of malignant tumors. The vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, is a specific mitogen for vascular endothelial cells. In the present case-control study, we carried out the study to evaluate whether the VEGF single-nucleotide polymorphisms play a role in modulating susceptibility to CRC. Methods: We evaluated the VEGF -2578A>C, +936C>T, and -460C>T genotypes obtained from 103 patients with CRC and 129 healthy controls by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Also, haplotype analysis was determined. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated. Results: -2578A>C was significantly associated with CRC risk (OR 1.81; 95% CI 0.94-3.47; p=0.0495), while distribution of +936C>T and -460C>T genotypes in cases and controls did not significantly differ. The VEGF A(2578)-T-936-T-460 haplotype might be associated with the development of CRC (OR 8.77; 95% CI 1.05-73.36; p=0.0434). There was significant haplotype effect for all eight haplotypes (p=0.02). Conclusions: These results suggest that the VEGF polymorphisms might play a role in the development of CRC. Therefore, the VEGF polymorphisms might be further investigated to use in the determination of risk factors for CRC and to have a predictive value for anti-VEGF-targeted cancer therapies

Expression of intracellular components of the NF-κB alternative pathway (NF-κB2, RelB, NIK and Bcl3) is associated with clinical outcome of NSCLC patients

A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P < 0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes