1. Inflammation and oxidative stress gene variability in retinal detachment patients with and without proliferative vitreoretinopathyXhevat Lumi, Filippo Confalonieri, Metka Ravnik-Glavač, Katja Goričar, Tanja Blagus, Vita Dolžan, Goran Petrovski, Marko Hawlina, Damjan Glavač, 2023, izvirni znanstveni članek Ključne besede: rhegmatogenous retinal detachment, proliferative vitreoretinopathy, single nucleotide polymorphism
Objavljeno v DiRROS: 03.09.2026; Ogledov: 95; Prenosov: 39
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2. Genetic variability of immune checkpoints in asbestos-related diseasesIrma Zeljković Vitas, Katja Goričar, Tanja Blagus, Alenka Franko, Viljem Kovač, Vita Dolžan, 2026, izvirni znanstveni članek Povzetek: Background Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying the development of asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases. Subjects and methods We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed using logistic regression. Results Our study showed that the CTLA4 rs4553808 polymorphism was associated with a decreased risk of asbestosrelated diseases (OR = 0.34, 95% CI = 0.15-0.74, P = 0.007). Homozygous carriers of polymorphic rs4553808 G allele had a lower risk of developing pleural plaques as well as MM compared to the control group (OR = 0.28, 95% CI = 0.11-0.68, P = 0.01, and OR = 0.38, 95% CI = 0.16 -0.93, P = 0.03, respectively). However, carriers of polymorphic CTLA4 rs231775 GG genotype had a higher risk of developing MM compared to the group of subjects with pleural plaques (OR = 1.79, 95% CI = 1.10-2.89, P = 0.02). The other investigated polymorphisms were not associated with any of the asbestos-related diseases. Conclusions CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases.
Ključne besede: asbestos, malignant mesothelioma, immune checkpoints, single nucleotide polymorphism
Objavljeno v DiRROS: 22.07.2026; Ogledov: 245; Prenosov: 132
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3. Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseasesAna Mervič, Katja Goričar, Tanja Blagus, Alenka Franko, Katarina Trebušak Podkrajšek, Metoda Dodič-Fikfak, Vita Dolžan, Viljem Kovač, 2024, izvirni znanstveni članek Povzetek: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM). Subjects and methods. We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis. Results. Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038). Conclusions. Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.
Ključne besede: malignant mesothelioma, asbestos, telomere length
Objavljeno v DiRROS: 26.06.2026; Ogledov: 280; Prenosov: 110
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4. Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristicsDavid Vogrinc, Sara Redenšek Trampuž, Tanja Blagus, Maja Trošt, Milica Gregorič Kramberger, Andreja Emeršič, Saša Čučnik, Katja Goričar, Vita Dolžan, 2024, izvirni znanstveni članek Povzetek: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ42/40 ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration.
Ključne besede: Alzheimer's disease, biomarker, glucagon-like peptide 1 receptor, glucose-dependent insulinotropic polypeptide, Parkinson's disease, polymorphism
Objavljeno v DiRROS: 09.06.2026; Ogledov: 282; Prenosov: 257
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5. Genetic variability in the glucocorticoid pathway and treatment outcomes in hospitalized patients with COVID-19 : a pilot studyPatricija Štampar, Tanja Blagus, Katja Goričar, Petra Bogovič, Gabriele Turel, Franc Strle, Vita Dolžan, 2024, izvirni znanstveni članek Povzetek: Introduction: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19. Genetic polymorphisms of the glucocorticoid receptor, metabolizing enzymes, or transporters may affect treatment response to dexamethasone. This study aimed to evaluate the association of the glucocorticoid pathway polymorphisms with the treatment response and short-term outcomes in patients with severe COVID-19. Methods: Our pilot study included 107 hospitalized patients with COVID-19 treated with dexamethasone and/or methylprednisolone, genotyped for 14 polymorphisms in the glucocorticoid pathway. Results: In total, 83% of patients had severe disease, 15.1% had critical disease and only 1.9% had moderate disease. CYP3A4 rs35599367 was the major genetic determinant of COVID-19 severity as carriers of this polymorphism had higher risk of critical disease (OR = 6.538; 95% confidence interval = 1.19-35.914: p = 0.031) and needed intensive care unit treatment more frequently (OR = 10; 95% CI = 1.754-57.021: p = 0.01). This polymorphism was also associated with worse disease outcomes, as those patients had to switch from dexamethasone to methylprednisolone more often (OR = 6.609; 95% CI = 1.137-38.424: p = 0.036), had longer hospitalization (p = 0.022) and needed longer oxygen supplementation (p = 0.040). Carriers of NR3C1 rs6198 polymorphic allele required shorter dexamethasone treatment (p = 0.043), but had higher odds for switching therapy with methylprednisolone (OR = 2.711; 95% CI = 1.018-7.22: p = 0.046). Furthermore, rs6198 was also associated with longer duration of hospitalization (p = 0.001) and longer oxygen supplementation (p = 0.001). NR3C1 rs33388 polymorphic allele was associated with shorter hospitalization (p = 0.025) and lower odds for ICU treatment (OR = 0.144; 95% CI = 0.027-0.769: p = 0.023). GSTP1 rs1695 was associated with duration of hospitalization (p = 0.015), oxygen supplementation and (p = 0.047) dexamethasone treatment (p = 0.022). Conclusion: Our pathway-based approach enabled us to identify novel candidate polymorphisms that can be used as predictive biomarkers associated with response to glucocorticoid treatment in COVID-19. This could contribute to the patient's stratification and personalized treatment approach.
Ključne besede: COVID-19, dexamethasone, glucocorticoid pathway, methylprednisolone, polymorphism, treatment outcome
Objavljeno v DiRROS: 08.06.2026; Ogledov: 348; Prenosov: 250
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6. Genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways: impact on the susceptibility and course of spinal muscular atrophyMaruša Barbo, Blaž Koritnik, Lea Leonardis, Tanja Blagus, Vita Dolžan, Metka Ravnik-Glavač, 2024, izvirni znanstveni članek Povzetek: The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients.
Ključne besede: inflammation, neurodegeneration, neurodevelopment, oxidative stress, single nucleotide polymorphism, spinal muscular atrophy
Objavljeno v DiRROS: 04.06.2026; Ogledov: 284; Prenosov: 254
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7. Immune infiltration, effector T-cell enrichment, and functional context for prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancerAna Demšar, Klara Geršak, Barbara Gazić, Tanja Blagus, Katja Goričar, Gregor Jezernik, Vita Dolžan, Cvetka Grašič-Kuhar, 2026, izvirni znanstveni članek Povzetek: Tumor-infiltrating lymphocytes (TILs) are an established predictor of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer. However, TILs primarily reflect the extent of immune infiltration and provide limited insight into immune functional state. We investigated whether integrating measures of immune infiltration (TILs), effector T-cell presence (CD8), and functional context (immune checkpoint components) may improve prediction of pCR beyond TILs alone. Pretreatment tumor biopsies from 166 patients with early breast cancer treated with standard NACT were assessed for stromal TILs and mRNA expression of CD8, PD-1, LAG-3, and TIM-3. Associations with pCR were evaluated using univariate and multivariable logistic regression, and composite immune phenotypes were constructed to capture functional immune states. In univariate analyses, higher TILs, CD8, PD-1, and LAG-3 were associated with pCR (all p < 0.05), whereas TIM-3 was not (p = 0.801). In multivariable models, TILs remained independently associated with pCR when adjusted for checkpoint markers, but this association was attenuated when CD8 was included, consistent with the strong biological correlation between TILs and CD8, and neither CD8 nor checkpoint markers retained independent significance. PD-1 and LAG-3 expression strongly correlated with CD8 and moderately correlated with TILs, indicating that checkpoint expression predominantly reflects an immune effector-engaged tumor microenvironment. Composite immune phenotypes based on CD8/PD-1 co-expression identified distinct immune functional states, with CD8-high/PD-1-high tumors demonstrating the highest pCR rates. Hierarchical modeling showed modest improvements in discrimination with sequential addition of immune variables to clinical predictors, with the integrative CD8/PD-1 model achieving the highest discrimination within the cohort (AUC = 0.849), although the magnitude of improvement beyond TIL assessment alone was limited. In conclusion, immune infiltration, effector T-cell presence, and functional immune context represent complementary dimensions for pCR prediction following NACT in breast cancer. However, TILs remain the most robust and clinically feasible immune biomarker.
Ključne besede: PD-1 immune checkpoint, breast cancer, immune microenvironment, neoadjuvant chemotherapy
Objavljeno v DiRROS: 20.04.2026; Ogledov: 411; Prenosov: 310
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8. Somatic mutation detection in tumor tissue and matched cell-free DNA using PCR-based methods in pancreatic cancer patients undergoing upfront resectionHana Zavrtanik, David Badovinac, Tanja Blagus, Katja Goričar, Branislava Ranković, Alenka Matjašič, Andrej Zupan, Aleš Tomažič, Vita Dolžan, 2025, izvirni znanstveni članek Povzetek: Somatic mutations in KRAS and TP53 are among the most common genetic alterations in pancreatic ductal adenocarcinoma (PDAC). Advances in PCR-based technologies now enable the detection of these mutations in tumor tissue and cell-free DNA (cfDNA), providing a minimally invasive approach to assess tumor burden. However, in resectable PDAC, circulating tumor DNA (ctDNA) may represent less than 0.1% of total cfDNA, requiring highly sensitive detection methods. The aim of our study was to assess two PCR-based assays—competitive allele-specific PCR (castPCR) and digital PCR (dPCR)—for detecting selected somatic mutations in tumor tissue, cfDNA, and extracellular vesicle-associated DNA (EV-DNA) from plasma. Matched primary tumor and preoperative plasma samples were collected from 50 patients undergoing upfront resection for PDAC. CastPCR was used for detecting selected KRAS, TP53, SMAD4, and CDKN2A mutations in tumor DNA. Additionally, dPCR was used to analyze KRAS and TP53 mutations in tumor DNA as well as cfDNA and EV-DNA. The concordance between both platforms was 71.4% for KRAS p.G12D and 58.3% for the analysis of TP53 p.R273H mutations in tumor tissue. However, dPCR detected these mutations in an additional 28.6% and 39.6% of samples, respectively. In cfDNA, dPCR identified KRAS p.G12D in 10.2% and TP53 p.R273H in 2.0% of samples. Mutation detection in EV-DNA was limited by low DNA yield. Both platforms proved effective for tumor DNA analysis, with dPCR offering greater sensitivity. Somatic mutation detection from liquid biopsy using dPCR further supports its potential utility in the preoperative setting.
Ključne besede: somatic mutation detection, cell-free DNA, liquid biopsy, digital PCR, pancreatic cancer
Objavljeno v DiRROS: 08.01.2026; Ogledov: 896; Prenosov: 405
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9. Association of matrix metalloproteinases polymorphisms with glaucoma risk, glaucoma phenotype, and response to treatment with selective laser trabeculoplasty or latanoprostMakedonka Atanasovska Velkovska, Katja Goričar, Tanja Blagus, Vita Dolžan, Barbara Cvenkel, 2024, izvirni znanstveni članek Povzetek: In open-angle glaucoma, the increase in intraocular pressure (IOP) is caused by an increased resistance to aqueous humour outflow in the trabecular meshwork. Since genetic variability of matrix metalloproteinase (MMP) genes may influence extracellular matrix remodelling, we investigated their association with glaucoma risk and/or response to treatment. The retrospective part of the study included patients with primary open-angle glaucoma and ocular hypertension (OHT); in the prospective part of the study, newly diagnosed patients with POAG or OHT were randomised to receive either latanoprost or selective laser trabeculoplasty (SLT) as the initial treatment. The reduction in IOP was measured 6 weeks after treatment. The following MMP single nucleotide polymorphisms were genotyped: MMP2 rs243865, rs243849, and rs7201; MMP3 rs3025058; MMP9 rs17576, rs17577, rs20544, and rs2250889; MMP14 rs1042704, rs1042704, and rs743257. Logistic regression was used to calculate odds ratios to assess the association between MMP polymorphism and risk of POAG or OHT, glaucoma phenotypes and response to treatment. Only carriers of the MMP3 rs3025058 TT genotype had a significantly higher risk of OHT, more advanced glaucoma, and a higher C/D ratio in the additive and dominant models. None of the investigated MMP polymorphisms were associated with response to treatment with latanoprost and SLT in our study population.
Ključne besede: glaucoma, latanoprost, matrix metalloproteinases, selective laser trabeculoplasty, single nucleotide polymorphisms
Objavljeno v DiRROS: 08.12.2025; Ogledov: 806; Prenosov: 387
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10. Genetic variability in sodium-glucose cotransporter 2 and glucagonlike peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practiceGašper Tonin, Katja Goričar, Tanja Blagus, Andrej Janež, Vita Dolžan, Jasna Klen, 2025, izvirni znanstveni članek Povzetek: We investigated the impact of genetic polymorphisms in the GLP1R and SLC5A2 genes on the response to treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose co-transporter-2 (SLGT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice.In our prospective interventional cohort open-label real-world genetic association study (DRKS-ID: DRKS00034478, https://drks.de/search/en/trial/DRKS00034478), we enrolled 161 clinically well-defined T2DM patients who received SGLT2 inhibitors and/or GLP-1R agonists alongside other medications for 3-6 months. The study's primary outcomes (HbA1c, body mass, and blood pressure) were measured before the treatment and at the follow-up at 3-6 months. GLP1R rs6923761, rs10305420, and SLC5A2 rs9934336 genotypes were determined by competitive allelespecific polymerase chain reaction. In patients receiving GLP-1R agonists, we analyzed the effect of GLP1R polymorphisms on the patients' response to treatment, while in patients receiving SGLT2 inhibitors, we analyzed the impact of the SLC5A2 polymorphism on the treatment effect.Treatment with prescribed antihyperglycemic drugs improved all primary outcomes (p < 0.050). The normal GLP1R rs6923761 G allele was associated with a greater reduction in HbA1c with GLP-1R agonists treatment than the polymorphic A allele in the dominant model (p = 0.029).The prevalent polymorphic A allele of GLP1R rs6923761 polymorphism was associated with the clinically relevant lower glycemic response to GLP-1R agonists. The described impact extends to everyday clinical practice, indicating that knowledge of these genetic polymorphisms could facilitate the development of targeted and personalized therapy in managing T2DM.
Ključne besede: polymorphism, type 2 diabetes, treatment response
Objavljeno v DiRROS: 17.11.2025; Ogledov: 652; Prenosov: 377
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