20.500.12556/DiRROS-29759 Genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways: impact on the susceptibility and course of spinal muscular atrophy 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. inflammation neurodegeneration neurodevelopment oxidative stress single nucleotide polymorphism spinal muscular atrophy vnetje nevrodegeneracija nevrološki razvoj oksidativni stres enojni nukleotidni polimorfizem spinalna mišična atrofija true false true Angleški jezik Slovenski jezik Neznano 2026-06-04 14:43:10 2026-06-04 14:43:11 2026-06-05 04:05:59 0000-00-00 00:00:00 2024 0 0 str. 1-18 iss. 1 Vol. 44 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8:577 0272-4340 10.1007/s10571-024-01508-y 215002883 RAZ_Barbo_Marusa_2024.pdf RAZ_Barbo_Marusa_2024.pdf 1 E7E44AD1E5371A50F22D35622376260C 959974f85ac85c8d6359d9fad38ab21dbaffcc27f975785fd8f7b7eed0899f35 0a00c683-6013-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44733 https://link.springer.com/article/10.1007/s10571-024-01508-y 1 f4f48b3c-6012-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44732 Univerzitetni klinični center Ljubljana 0 0 0