Could MMP3 and MMP9 Serve as Biomarkers in EBV-Related Oropharyngeal Cancer.

The high incidence of, and mortality from, head and neck cancers (HNCs), including those related to Epstein-Barr virus (EBV), constitute a major challenge for modern medicine, both in terms of diagnosis and treatment. Therefore, many researchers have made efforts to identify diagnostic and prognostic factors. The aim of this study was to evaluate the diagnostic usefulness of matrix metalloproteinase 3 (MMP 3) and matrix metalloproteinase 9 (MMP 9) in EBV positive oropharyngeal squamous cell carcinoma (OPSCC) patients. For this purpose, the level of these MMPs in the serum of patients with EBV-positive OPSCC was analyzed in relation to the degree of histological differentiation and TNM classification. Our research team's results indicate that the level of both MMPs is much higher in the EBV positive OPSCC patients compared to the EBV negative and control groups. Moreover, their levels were higher in more advanced clinical stages. Considering the possible correlation between the level of MMP 3, MMP 9 and anti-EBV antibodies, and also viral load, after statistical analysis using multiple linear regression, their high correlation was demonstrated. The obtained results confirm the diagnostic accuracy for MMP 3 and MMP 9. Both MMPs may be useful in the diagnosis of EBV positive OPSCC patients.

Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors.

µ-opioid receptor ligands such as morphine and fentanyl are the most known and potent painkillers. However, the severe side effects seen with their use significantly limit their widespread use. The continuous broadening of knowledge about the properties of the interactions of the MOP receptor (human mu opioid receptor, OP3) with ligands and specific intracellular signaling pathways allows for the designation of new directions of research with respect to compounds with analgesic effects in a mechanism different from classical ligands. Allosteric modulation is an extremely promising line of research. Compounds with modulator properties may provide a safer alternative to the currently used opioids. The aim of our research was to obtain a series of urea derivatives of 1-aryl-2-aminoimidazoline and to determine their activity, mechanism of biological action and selectivity toward the MOP receptor. The obtained compounds were subjected to functional tests (cAMP accumulation and ß-arrestin recruitment) in vitro. One of the obtained compounds, when administered alone, did not show any biological activity, while when co-administered with DAMGO, it inhibited ß-arrestin recruitment. These results indicate that this compound is a negative allosteric modulator (NAM) of the human MOP receptor.

AOTMiT reimbursement recommendations compared to other HTA agencies.

Our objective was to compare AOTMiT (Polish: Agencja Oceny Technologii Medycznych i Taryfikacji) recommendations to other HTA (Health Technology Assessment) agencies for newly registered drugs and new registration indications issued by the European Medicines Agency between 2014 and 2019. The study aims to assess the consistency and justifications of AOTMiT recommendations compared to that of other HTA agencies in 11 countries. A total of 2494 reimbursement recommendations published by 12 HTA agencies for 464 medicinal products and 525 indications were analyzed. Our analysis confirmed that the Polish AOTMiT agency seems to bear the closest resemblance to the corresponding HTA agencies from Canada (CADTH) and New Zealand (PHARMAC), when it comes to the outcome of HTA recommendations (positive or negative). Poland had a general scheme for justifying recommendations, similar to that of Ireland-four aspects (i.e., clinical efficacy, safety profile, cost-effectiveness, and impact on the payer's budget) are important for Poland when formulating the final decision. Compared to other countries, Poland shows a noticeably different pattern of justifying reimbursement recommendations, as revealed primarily in terms of budget impact and somewhat less so for cost-effectiveness rationales.

Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer?

Prostate cancer (PCa) is the fourth most frequently diagnosed cancer worldwide, accounting for 7.3% of all cancers. PCa mortality is the fifth most common cause of cancer death. Despite well-known factors influencing the development of PCa, such as age, race/ethnicity and family history, many researchers have raised the possibility of persistent infections with oncogenic viruses. Therefore, we aimed to assess the frequency of Epstein-Barr virus (EBV) DNA in tissue collected from PCa patients. Next, the frequency and the level of Epstein-Barr virus capsid antigen (EBVCA) and Epstein-Barr nuclear antigen 1 (EBNA1) antibodies in both IgA and IgG classes were measured. The antibody titer was also analyzed depending on the risk group, Gleason score (GS) and tumor, node, metastasis (TNM) classification. Serum samples were analyzed using the Microblot-Array EBV IgM, IgA and IgG test kits. The study group consisted of 115 patients diagnosed and histopathologically confirmed with PCa. In 49% of patients included in the study, EBV DNA was detected in the tumor tissue. The studies showed both higher seroprevalence and higher antibody titers in patients with EBV-positive PCa compared to patients with EBV-negative PCa. We also observed a dependence of antibody titer on pathological features, such as GS, risk group and T stage.

Serum Anti-Zta and Anti-LMP1 Antibodies in Oropharyngeal Cancer Related to Epstein-Barr Virus-Diagnostic Usefulness.

BACKGROUND: The role of the Epstein-Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to the lack of an effective vaccine against EBV, it is necessary to search for new markers for the early diagnosis and prognosis of this disease. The aim of current study was to determine the usefulness of anti-Zta and anti-LMP1 antibodies as diagnostic and prognostic markers in EBV positive OPSCC patients. METHODS: For this purpose, experiments were carried out to determine both the prevalence and level of EBVCA, EBNA1, EA, Zta, and LMP1 antibodies in serum patients depending on histological differentiation-grading and TNM classification (ELISA assay). RESULTS: Based on the obtained results, we showed that OPSCC EBV positive patients are characterized by a higher level of anti-Zta antibodies than in the EBV negative group. Their level depended on the clinical stage. Moreover, a ROC analysis confirmed the diagnostic accuracy of anti-Zta antibodies. CONCLUSIONS: Anti-Zta and anti-LMP1 antibodies may be useful in the diagnosis of OPSCC. It seems that combined antibody testing should be performed to increase diagnostic accuracy.

Assessment of Awareness and Knowledge about Osteoporosis in Relation to Health Prevention among Patients Treated in Osteoporosis Clinics.

The increasing incidence of osteoporosis indicates that the disease is a serious public health problem, with about 200 million people being affected worldwide. The aims of this research are to assess the awareness and knowledge about osteoporosis in relation to risk factors, health condition, supplementation used, socio-demographic factors and other variables among osteoporosis patients. The study was conducted in 2016-2018 in osteoporosis clinics in Poland. The study involved 312 patients with a diagnosis of osteoporosis. In the diagnostic survey method, the authors' own questionnaire was used. The results indicate that the more frequent the symptoms associated with the disease, the lower the general self-assessment of the health condition of the respondents (rho = -0.682, p < 0.001). In addition, almost half of the respondents stated that their knowledge of osteoporosis is negligible. Moreover, the use of dietary supplements significantly differentiated respondents in terms of health self-assessed (p < 0.001), and it is noteworthy that users of dietary supplements assessed their health significantly better. We also saw a statistically significant relationship between the self-assessment of knowledge about osteoporosis and the use of dietary supplements (p < 0.001). Accordingly, significantly more respondents rating their knowledge as good or very good used dietary supplements. The conducted study demonstrates the need to educate patients and implement educational programs at central and provincial levels to improve patient knowledge concerning the disease. Supporting adaptation to chronic diseases and appropriate therapeutic management may contribute to improved osteoporosis treatment and enhanced patient quality of life.

Serum and Saliva Level of miR-31-5p and miR-let 7a in EBV Associated Oropharyngeal Cancer.

Epstein-Barr virus (EBV) has a well-documented association with head and neck neoplasms, including nasopharyngeal carcinoma (NPC). In the last few years, research aimed at elucidating the role of the miRs in the pathogenesis of head and neck cancer (HNC) has gained importance. The study of miRs expression has set new directions in the search for biomarkers with diagnostic and prognostic value, and even in the search for new therapeutic targets for various tumors, including HNC. The aim of current study was to approximate the importance of miR-31-5p and miR-let 7a in the pathogenesis of EBV associated oropharyngeal cancer. For this purpose, experiments were carried out to determine the level of mentioned miRs in serum among patients diagnosed with oropharyngeal cancer linked to EBV infection, depending on histological differentiation-grading (G1-G3) and TNM classification. All clinical specimens stratified by HPV status were HPV negative. The level of antibodies EBNA and EBVCA was also assessed. The obtained results showed a significantly increased serum level of miR-31-5p but decreased level of miR-let 7a in EBV positive oropharyngeal cancer patients. We demonstrated association between the level of tested miRs and clinical stage. Our findings showed that miR-31-5p and miR-let-7a may be involved in development and progression of EBV associated oropharyngeal cancer. Therefore, it seems important to further study these molecules, as well as to determine whether they could be important biomarkers in the diagnosis of oropharyngeal cancer associated with EBV infection.

Humoral Response after SARS-CoV-2 Vaccination in Prostate Cancer Patients.

Cancer is an important public health problem. Prostate cancer is one of the most common cancers among men. In Poland, the incidence of this type of cancer is constantly growing. Considering the appearance of a new coronavirus in December 2019 (SARS-CoV-2) and the fact that oncology patients, including those with prostate cancer, are particularly vulnerable to infection, it is recommended to get vaccinated against COVID-19. In our study, we determined the level and prevalence of antibodies against SARS-CoV-2 IgG in patients with prostate cancer compared to the control group and whether the patients' ages affected the level of antibodies. PCa patients and controls were divided into two age groups: 50-59 years and 60-70 years. We also analyzed the level of antibodies in patients belonging to the relevant risk groups for prostate cancer (the European Society of Urology risk group classification of prostate cancer). For the study, we used the Microblot-Array COVID-19 IgG test to detect antibodies against the three main SARS-CoV-2 antigens: NCP, RBD, and S2. Our results showed that prostate cancer patients had significantly lower levels of anti-SARS-CoV-2 IgG antibodies compared to controls. In addition, age also affected the decrease in the number of IgG antibodies. The level of antibodies in the intermediate/high-risk group was lower compared to the low-risk group.

MiRNA-21-5p as a biomarker in EBV-associated oropharyngeal cancer.

INTRODUCTION AND OBJECTIVE: Epstein-Barr virus (EBV) is associated with cancers of the head and neck, including oropharyngeal cancer, which is increasing in incidence, and biomarker studies have potential in diagnostics and therapy. One of the most commonly deregulated microRNAs in cancers is miR-21-5p. It has been implicated in neoplastic transformation related to EBV infection in several investigations. The aim of this study was to determine the level of miR-21-5p in the serum of EBV (+) and EBV (-) oropharyngeal cancer patients. MATERIAL AND METHODS: The study was carried out on 78 patients with confirmed OPSCC. Statistical analysis was used to investigate the relationship between clinical and demographic characteristics of patients. Enzyme immunoassays were used to determine the levels of miRNA, TLR9 and MMPs and cytokines. Statistical analysis was used to determine the relationship between miR21-5p and TLR9, MMP3, MMP9 levels, and the cytokines studied. RESULTS: Significantly higher values of all tested parameters for miR-21-5p levels and grading as well as TN stage were found in the EBV (+) group. There was no statistically significant correlation between the miR-21-5p level and the levels of TNFα, VEGF, and TGFß. Positive correlations were shown between miR-21-5p and IL-10, MMP-3 and -9. There was a negative correlation between the level of miR-21-5p and TLR9. CONCLUSIONS: The present study showed that in EBV (+) patients the level of miR-21-5p in the serum was significantly higher than in EBV (-) patients. Our study results could influence future strategies for the diagnosis, prevention and treatment of oropharyngeal cancers.

Colorectal Cancer-The Worst Enemy Is the One We Do Not Know.

BACKGROUND: Colorectal cancer is one of the most common cancers in humans. It is the third most frequently diagnosed malignant neoplasm and is the second highest cause of cancer mortality in the world. Every year, more and more people die of colorectal cancer because the diagnosis is conducted too late. This shows how important a role screening tests and the awareness of the population about the symptoms play in this aspect. This article aimed to determine the knowledge of the Polish population about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. METHODS: In 2020, a study was conducted using an online questionnaire assessing the awareness of the Polish population about colorectal cancer. A self-authored questionnaire including questions about socio-demographic characteristics, and 18 questions related to substantive issues, was used. A research group was selected (n = 633). The substantive part of the questionnaire included questions examining the respondents' knowledge about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. RESULTS: The respondents' awareness level was influenced by demographic factors, such as gender: (p < 0.05) and age (p < 0.05) and social factors, such as: level of education (p < 0.05) or professional situation (p < 0.05). Compared to thematic articles from other countries, the research group was divided into smaller subgroups due to the abovementioned factors, due to which it was possible to stratify and analyze the significance of differences between them.

Serum Level of MMP-3 and MMP-9 in Patients with Diabetes Mellitus Type 2 Infected with Epstein-Barr Virus.

Diabetes mellitus type 2 (DM2) has recently become one of the most important health problems in the world. Patients with DM2 with long-term glycaemia are more likely to become infected than the healthy population. Matrix metalloproteinases (MMPs) play a key role in tissue remodeling during various physiological processes. However, it has been reported that certain MMPs are overexpressed during the development of various human diseases. In this study, we analyzed the levels of MMP-3 and MMP-9 in the serum of DM2 patients with and without Epstein-Barr virus (EBV) infection. The study included 115 patients with DM2 hospitalized in the Internal Ward of the Masovian Specialist Hospital in Radom, Poland, who were divided into two groups: EBV-positive and EBV-negative. The levels of MMP-3 and MMP-9 were tested in the serum of patients using the ELISA method, while the presence of EBV in saliva was tested by polymerase chain reaction (PCR). The presented studies showed a significant difference in the concentration of both MMPs in diabetic patients additionally infected with EBV compared to the group of non-infected individuals. It seems that MMPs may be useful biomarkers in the diagnosis, prognosis, and monitoring of diabetes associated with EBV infection.

Antibody Response after SARS-CoV-2 Infection with the Delta and Omicron Variant.

The SARS-CoV-2 virus caused a worldwide COVID-19 pandemic. So far, 6,120,834 confirmed cases of COVID-19 with 116,773 deaths have been reported in Poland. According to WHO, a total of 54,662,485 vaccine doses have been administered. New variants emerge that become dominant. The aim of this study was a comparison of antibody level after infection caused by Delta and Omicron variants. The study included 203 persons who underwent mild COVID-19 despite two doses of vaccine. The obtained results indicate that a significantly lower titer was observed in patients with the Omicron variant infection. Therefore, these patients may be at risk of reinfection with new strains of the Omicron variant. Due to the possibility of reinfection, booster vaccinations are necessary. Further epidemiological and clinical studies are necessary to develop new prevention strategies.

Antibodies to NCP, RBD and S2 SARS-CoV-2 in Vaccinated and Unvaccinated Healthcare Workers.

In a few months, the SARS-CoV-2 virus caused a worldwide COVID-19 pandemic. In Poland, 6 million cases of the disease and 113,000 deaths from COVID-19 have been reported. Healthcare workers (HCWs) constitute one of the main COVID-19 risk groups. The Microblot-Array COVID-19 IgG assay was used to detect antibodies against three major SARS-CoV-2 antigens: nucleocapsid (NCP), RBD, and Spike 2 (S2). The aim of our study was to determine the seroprevalence and titer of anti-SARS-CoV-2 IgG antibodies-NCP, RBD, and S2-as markers of the humoral response in vaccinated and unvaccinated HCWs. The study included 203 persons who were divided into four groups: "COVID-19 Vaccinated", "COVID-19 Unvaccinated", "Non-COVID-19 Vaccinated", and "Non-COVID-19 Unvaccinated". The obtained results indicate that both seroprevalence and the antibody titer are the highest in the "COVID-19 Vaccinated" group. There is no so-called sterile vaccination, and after 6 months from the second dose of vaccine, most vaccinated people have a fairly high level of antibodies. We suggest that multiple vaccination and continuous testing are necessary. The Microblot-Array assay can distinguish between antibodies acquired after infection and/or vaccination.

Assessment of the Level of Satisfaction with Medical Care of Patients Treated in Osteoporosis Clinics as an Indicator of the Quality of Medical Care.

The aims of this research are to assess the level of satisfaction with medical care among patients treated in osteoporosis clinics and to determine the relationship among the frequency of visits to the doctor, the duration of treatment, socio-demographic factors, and patient satisfaction with the medical care they receive. The study was conducted from August 2016 to July 2018 at osteoporosis clinics in eastern Poland. The study participants were 312 patients treated for osteopenia or osteoporosis. The authors utilized two research instruments: the PASAT POZ questionnaire and their own questionnaire. The results indicate that the duration of osteoporosis treatment is a factor that significantly influences the level of satisfaction with medical care: the longer the treatment time, the poorer the assessment of the clinic, and therefore, the lower the patient degree of satisfaction. Our analysis shows that women assess clinics more positively overall. Additionally, the higher the study participants' age, the lower the general assessment of the clinic. A further analysis showed that respondents in better financial situations and with higher levels of education tended to assess clinics more favorably. The Pareto-Lorenz analysis indicated that the key element in general assessments of specialist clinics is the doctor. It is advisable for health service providers to monitor the quality of health care they are providing and make improvements. Therefore, further research is needed, especially in relation to chronic diseases such as osteoporosis.

Coping Strategies Preferred by Patients Treated for Osteoporosis and Analysis of the Difficulties Resulting from the Disease.

Osteoporosis has been recognized as a civilization disease. This chronic condition needs a long-term management plan with a holistic approach to patients. The specificity of the patient's response to the disease and coping strategies are very important in the treatment process. The aim of this research was to analyze the strategies of coping with disease preferred by patients treated for osteoporosis, and to determine the relationship between the self-assessment of patients' health, time of treatment, sociodemographic variables, and strategies of coping with a chronic disease such as osteoporosis. The study was conducted from August 2016 to July 2018 at an osteoporosis clinic in eastern Poland. Coping Orientations to Problems Experienced (COPE) by C.S. Carver, M. F. Scheier, and J. K. Weintraub in the Polish adaptation and our own questionnaire were used. The study participants were 312 patients treated for osteoporosis. The respondents treated in the osteoporosis clinic used the strategies of seeking support and focusing on emotions to the greatest extent, and avoidance strategies the least. Sociodemographic features and self-assessment of health condition significantly differentiate the strategies of coping with the disease. The analysis showed that the higher the assessment of the individual perception of one's own health, the more often the respondents used active coping strategies.

Modulation of the MOP Receptor (µ Opioid Receptor) by Imidazo[1,2-a]imidazole-5,6-Diones: In Search of the Elucidation of the Mechanism of Action.

The µ-opioid receptors belong to the family of G protein-coupled receptors (GPCRs), and their activation triggers a cascade of intracellular relays with the final effect of analgesia. Classical agonists of this receptor, such as morphine, are the main targets in the treatment of both acute and chronic pain. However, the dangerous side effects, such as respiratory depression or addiction, significantly limit their widespread use. The allosteric centers of the receptors exhibit large structural diversity within particular types and even subtypes. Currently, a considerable interest is aroused by the modulation of µ-opioid receptors. The application of such a technique may result in a reduction in the dose or even discontinuation of classical opiates, thus eliminating the side effects typical of this class of drugs. Our aim is to obtain a series of 1-aryl-5,6(1H)dioxo-2,3-dihydroimidazo[1,2-a]imidazole derivatives and provide more information about their activity and selectivity on OP3 (MOP, human mu opioid receptor). The study was based on an observation that some carbonyl derivatives of 1-aryl-2-aminoimidazoline cooperate strongly with morphine or DAMGO in sub-threshold doses, producing similar results to those of normal active doses. To elucidate the possible mechanism of such enhancement, we performed a few in vitro functional tests (involving cAMP and ß-arrestin recruitment) and a radioligand binding assay on CHO-K1 cells with the expression of the OP3 receptor. One of the compounds had no orthosteric affinity or intrinsic activity, but inhibited the efficiency of DAMGO. These results allow to conclude that this compound is a negative allosteric modulator (NAM) of the human µ-opioid receptor.

Adjustment in women treated for rheumatoid arthritis.

INTRODUCTION: The favourable or unfavourable process of a patient's adaptation to a challenging medical condition may indicate that certain adjustment reactions, which can be either constructive or undesirable, tend to prevail. OBJECTIVE: The aim of the study was to examine the adjustment reactions of patients, and to define the correlation between the reactions and socio-demographic factors, health self-assessment, satisfaction with medical care, duration of treatment, and limitations in women treated for rheumatoid arthritis. MATERIAL AND METHODS: The study was conducted at the Department of Rheumatology and Connective Tissue Diseases and the Specialist Outpatient Clinic of the Independent Public Teaching Hospital No. 4 in Lublin, Poland. The Polish adaptation of the Reactions to Impairment and Disability Inventory RIDI (H. Livneh, R. Antonak, 1990) was used in the study, together with an Original Questionnaire. A p-value of <0.05 was set to define statistical differences. Analysis was performed using commercial SPSS Statistics software (IBM Corp., Armonk, NY). RESULTS: Adjustment reactions, adaptive reactions, i.e. adjustment (3±0.5) and acknowledgement (2.6±0.4) were found to markedly prevail, while the lowest mean value was observed for denial (1.9±0.4), which was considered a negative reaction. Longer duration of the disease was associated with a lower level of external hostility. Low health self-assessment and significant limitations impairing everyday activities, caused by pain, deformity and impaired joint mobility, were mostly related to unfavourable early and intermediate non-adaptive reactions. CONCLUSIONS: Knowledge of the adjustment reactions and their moderating factors appears to be crucial in the planning of measures aimed at the rehabilitation of RA patients.

SARS-CoV-2 Infection Prevalence in the Population of South-Eastern Poland.

COVID-19 outbreak began in Wuhan, China, and has spread to other continents, including Europe, placing pressure on healthcare systems. Poland is one of the European countries with the highest number of SARS-CoV-2 infections and COVID-19-related deaths. The aim of this study was to analyze the presence of SARS-CoV-2 in the population of south-eastern Poland. The correlation between viral infection and demographic data (gender, age, place of residence) and cancer was also investigated. A total of 44,801 samples were tested, of which 4862 cases were diagnosed with SARS-CoV-2 infections. A total of 14,970 samples were tested in cancer patients. The RT-PCR method was used to detect viral nucleic acid. In this study, significantly, the highest rate of virus detection was among people living in Lublin and the lowest among people living in a small town (p < 0.0001). Moreover, there was no significant relationship between sex and the frequency of virus detection. The highest number of SARS-CoV-2 infections was observed in the age groups 10-19, 20-29, 30-39, and 90+ (p = 0.0001). In cancer patients, the percentage of positive cases was significantly lower than in the rest (p = 0.0001).

Serum and Tissue Level of TLR9 in EBV-Associated Oropharyngeal Cancer.

The Epstein-Barr virus (EBV) is associated with the development of various epithelial malignancies including cancer in the head and neck region. Several studies have shown that Toll-like receptors (TLRs) are required for an innate immune response to infection with human DNA viruses, e.g., EBV. During viral infections, TLR response may influence the transformation to malignancy. The aim of the study was to assess TLR9 serum and tissue level in EBV(+) and EBV(-) oropharyngeal cancer patients. The study involved 78 patients: 42 EBV(+) and 36 EBV(-). EBV DNA was detected in fresh frozen tumor tissue. TLR9 level was measured in homogenate of tumor tissue and in serum. Moreover, in serum samples IL-10, VEGF, TGFß, TNFα and antibodies against EBV were detected using ELISA test. TLR9 level was significantly lower in EBV(+) patients, both in tissue and serum, while EBVCA, EBNA and VEGF level was statistically higher in EBV(+) patients. An increase in EBVCA and EBNA antibodies titer was correlated with a TLR9 level decrease. TLR9 level was higher in poorly-differentiated tumors (G3), in tumor of larger dimensions (T3-T4) and with lymph nodes involvement (N3-N4) but without statistical significance. High levels of anti-EA antibodies in the majority of EBV(+) patients may point to the reactivation of EBV infection.

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus.

AIMS: Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). METHODS: In this case-control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN- (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR- (independently of the presence of DN). RESULTS: No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16-1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26-2.75, p = 0.001) than DR- patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). CONCLUSIONS: This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.