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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 <jats:italic>TNF<\/jats:italic> rs1800629 and <jats:italic>BDNF<\/jats:italic> rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the <jats:italic>IL6<\/jats:italic> rs1800795 was associated with an increased risk. The polymorphisms <jats:italic>CARD8<\/jats:italic> rs2043211 and <jats:italic>BDNF<\/jats:italic> rs6265 were associated with SMA type, while <jats:italic>SOD2<\/jats:italic> rs4880, <jats:italic>CAT<\/jats:italic> rs1001179, and <jats:italic>MIR146A<\/jats:italic> rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, <jats:italic>GPX1<\/jats:italic> rs1050450 and <jats:italic>HMOX1<\/jats:italic> rs2071747 were associated with motor function scores and lung function scores, while <jats:italic>MIR146A<\/jats:italic> rs2910164, <jats:italic>NOTCH<\/jats:italic> rs367398 SNPs, and <jats:italic>GSTM1<\/jats:italic> deletion were associated with motor and upper limb function scores, and <jats:italic>BDNF<\/jats:italic> 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.<\/jats:p>","DOI":"10.1007\/s10571-024-01508-y","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T08:53:42Z","timestamp":1730105622000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy"],"prefix":"10.1007","volume":"44","author":[{"given":"Maru\u0161a","family":"Barbo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bla\u017e","family":"Koritnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Leonardis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Blagus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Dol\u017ean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metka","family":"Ravnik-Glava\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,27]]},"reference":[{"issue":"7","key":"1508_CR1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.3390\/genes13071237","volume":"13","author":"EK Abdalhabib","year":"2022","unstructured":"Abdalhabib EK, Algarni A, Saboor M, Alanazi F, Ibrahim IK, Alfeel AH, Alanazi AM, Alanazi AM, Alruwaili AM, Alanazi MH, Alshaikh NA (2022) Association of TNF-\u03b1 rs1800629 with Adult Acute B-Cell Lymphoblastic Leukemia. 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