Genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways: impact on the susceptibility and course of spinal muscular atrophy

Barbo, Maruša (author), Koritnik, Blaž (author), Leonardis, Lea (author), Blagus, Tanja (author), Dolžan, Vita (author), Ravnik-Glavač, Metka (author)

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.

• Language: English
• Keywords: inflammation, neurodegeneration, neurodevelopment, oxidative stress, single nucleotide polymorphism, spinal muscular atrophy
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 18 str.
• Numbering: Vol. 44, iss. 1, art. 71
• PID: 20.500.12556/RUL-164909
• UDC: 616.8:577
• ISSN on article: 0272-4340
• DOI: 10.1007/s10571-024-01508-y
• COBISS.SI-ID: 215002883
• Publication date in RUL: 15.11.2024

Record is a part of a journal

• Title: Cellular and molecular neurobiology
• Shortened title: Cell. mol. neurobiol.
• Publisher: Springer Nature
• ISSN: 0272-4340
• COBISS.SI-ID: 467476

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: vnetje, nevrodegeneracija, nevrološki razvoj, oksidativni stres, enojni nukleotidni polimorfizem, spinalna mišična atrofija

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARIS - Slovenian Research and Innovation Agency
• Funding programme: Young researchers