1. GiOPARK Project : the genetic study of Parkinson’s Disease in the Croatian populationValentino Rački, Gaber Bergant, Eliša Papić, Anja Kovanda, Mario Hero, Gloria Rožmarić, Nada Starčević-Čizmarević, Smiljana Ristić, Saša Ostojić, Miljenko Kapović, Aleš Maver, Borut Peterlin, Vladimira Vuletić, 2024, original scientific article Keywords: Parkinson’s disease, genetic testing, whole-exome sequencing
Published in DiRROS: 09.06.2026; Views: 280; Downloads: 163
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2. CCR5 Δ32 and CTLA-4 +49 A/G gene polymorphisms and interferon-β treatment response in Croatian and Slovenian multiple sclerosis patientsJasna Nekić, Ivana Stanković Matić, Valentino Rački, Dolores Janko Labinac, Vladimira Vuletić, Miljenko Kapović, Smiljana Ristić, Borut Peterlin, Nada Starčević-Čizmarević, 2024, original scientific article Abstract: The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and nonresponders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.
Keywords: multiple sclerosis, polymorphism, treatment response, interferon-β
Published in DiRROS: 10.03.2026; Views: 398; Downloads: 221
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3. Microbial diversity in drug-naïve Parkinson’s disease patientsEliša Papić, Valentino Rački, Mario Hero, Ana Nyasha Zimani, Mojca Čižek-Sajko, Gloria Rožmarić, Nada Starčević-Čizmarević, Saša Ostojić, Miljenko Kapović, Goran Hauser, Aleš Maver, Borut Peterlin, Anja Kovanda, Vladimira Vuletić, 2025, original scientific article Abstract: Parkinson’s disease (PD) is a neurological disorder characterized by rigidity, bradykinesia and tremor. Several genetic and environmental causes of PD are known, and there is emerging evidence of the possible contribution of the gut microbiome to the disease onset, severity, and response to therapy. While previous research has shown several differences in the microbiome of PD patients under therapy as opposed to healthy controls, few prospective studies have included drug-naïve patients. In order to evaluate the gut microbiome composition prior to therapy initiation, we collected and performed 16S rRNA gene sequencing of the stool samples from 49 drug-naïve PD patients and compared them to 34 diet and lifestyle-matched controls from the Croatian population (GiOPARK Project). While no significant alpha diversity difference was observed between the patients and controls, the differential relative abundance analysis showed an increase in Bacteroides fluxus, B. interstinalis, B. eggerthii, and Dielma fastidiosa in the drug-naïve PD patients compared to controls, while Alistipes, Barnesiella and Dialister spp. were decreased in patients compared to controls. Despite preserved overall diversity, these changes may indicate early microbial dysbiosis and represent a foundation for future studies exploring microbiome changes across disease progression and treatment.
Keywords: Parkinson’s disease, neurological disorder, gut microbiome, microbial diversity, microbial dysbiosis
Published in DiRROS: 23.02.2026; Views: 574; Downloads: 281
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4. Increased burden of rare variants in GWAS associated genes in familial multiple sclerosisAleksander Turk, Aleš Maver, Peter Juvan, Jelena Drulović, Sarlota Mesaros, Ivana Novaković, Nada Starčević-Čizmarević, Smiljana Ristić, Ivana Stanković Matić, Borut Peterlin, 2025, original scientific article Abstract: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease affecting the central nervous system with many known genetic risk factors. Although genome-wide association studies (GWAS) have identified common genetic variants with small effects associated with MS, the role of rare variants with large effects in MS aetiology remains underexplored. We hypothesized that rare variants in MS-associated genes from GWAS studies (GWAS-associated genes) are more likely to contribute to familial MS (FMS) risk than to sporadic MS (SMS). Therefore, we aimed to assess the burden of rare, predicted pathogenic (RPP) variants in GWAS-associated genes in FMS and SMS patients compared to controls. Rare genetic variants in 111 GWAS-associated genes were assessed in 87 FMS, 89 SMS and 3866 control cases. We demonstrate that RPP variants were significantly overrepresented in the FMS cohort whereas their frequency was not increased in the SMS cohort compared to controls (p-values 5.27 × 10− 74 and 1.00, respectively). Six genes (ALPK2, ANKRD55, INTS8, IQCB1, JADE2, and MALT1) significantly contributed to the burden of RPP in the FMS group. We conclude that rare variants in genes identified by GWAS might contribute to the genetic predisposition of familial MS patients.
Keywords: multiple sclerosis, burden analysis, whole exome sequencing (WES), rare variants, rare pathological changes, candidate genes
Published in DiRROS: 12.11.2025; Views: 583; Downloads: 335
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