{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:29:44Z","timestamp":1760059784409,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2019\/35\/O\/NZ5\/02270"],"award-info":[{"award-number":["2019\/35\/O\/NZ5\/02270"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and neurodegeneration. While its etiology remains unclear, both genetic and environmental factors, including oxidative stress, have been implicated in the development of the disease. The base excision repair (BER) pathway plays a critical role in repairing oxidative DNA damage. This study investigated the association between polymorphisms in BER-related genes and MS susceptibility in a Central European population. Ten SNPs across seven BER genes were genotyped in 102 patients with MS and 118 healthy controls. Six SNPs were significantly associated with MS. Increased risk was observed for rs25478 in XRCC1 (OR = 2.37, 95% CI: 1.44\u20133.91, p &lt; 0.0001), rs3087404 in SMUG1 (OR = 2.80, 95% CI: 1.49\u20135.26, p = 0.0012), and rs3219493 in MUTYH (OR = 2.23, 95% CI: 1.35\u20133.67, p = 0.0018). Conversely, reduced risk was associated with rs2307293 in MBD4 (OR = 0.42, 95% CI: 0.23\u20130.78, p = 0.006), rs3219489 in MUTYH (OR = 0.55, 95% CI: 0.31\u20130.97, p = 0.038), and rs4135054 in TDG (OR = 0.52, 95% CI: 0.29\u20130.94, p = 0.031). Haplotype analysis was performed for SNPs in strong linkage disequilibrium. Only rs3219489 and rs3219472 within the MUTYH gene showed strong LD (r2 = 0.90), justifying haplotype-based analysis. Among four inferred haplotypes, the rare G\u2013C haplotype was significantly associated with reduced MS risk (Score = \u22122.10, p = 0.035), suggesting a protective effect of this allele combination. Other SNPs not in LD were analyzed using a multivariable logistic regression model. Significant associations with decreased MS risk were found for rs1052133 in OGG1 (OR = 0.57, p = 0.043), rs2307293 in MBD4 (OR = 0.16, p = 0.010), and rs4135054 in TDG (OR = 0.38, p &lt; 0.001), while rs3087404 in SMUG1 increased MS risk (OR = 1.98, p = 0.013). These results suggest that genetic variation in BER genes, including both single SNP effects and haplotypes, contributes to MS susceptibility. Further studies are warranted to explore the functional consequences of these variants and validate findings in larger, independent cohorts.<\/jats:p>","DOI":"10.3390\/ijms26146612","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:46:33Z","timestamp":1752237993000},"page":"6612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymorphisms in Base Excision Repair Genes and Association with Multiple Sclerosis in a Pilot Study on a Central European Population"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-5650","authenticated-orcid":false,"given":"Beata","family":"Filipek","sequence":"first","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"},{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6056-7808","authenticated-orcid":false,"given":"Anna","family":"Macieja","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6173-4525","authenticated-orcid":false,"given":"Aleksandra","family":"Binda","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7029-1857","authenticated-orcid":false,"given":"Elzbieta","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-308X","authenticated-orcid":false,"given":"Mariola","family":"Swiderek-Matysiak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-1708","authenticated-orcid":false,"given":"Mariusz","family":"Stasiolek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maksymilian","family":"Stela","sequence":"additional","affiliation":[{"name":"Biohazard Prevention Centre, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ireneusz","family":"Majsterek","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-7339","authenticated-orcid":false,"given":"Tomasz","family":"Poplawski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100977","DOI":"10.1016\/j.lanepe.2024.100977","article-title":"Multiple sclerosis: Emerging epidemiological trends and redefining the clinical course","volume":"44","author":"Portaccio","year":"2024","journal-title":"Lancet Reg. 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