{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T08:36:23Z","timestamp":1773477383404,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Aim: The purpose of this work was to investigate the prevalence of SIRT1 rs3818292, rs3758391, and rs7895833 single nucleotide polymorphisms and SIRT1 serum levels associated with multiple sclerosis (MS) in the Lithuanian population. Methods: A total of 250 MS patients and 250 healthy controls were included in the study. Genotyping was performed using the RT-PCR method. Statistical analysis was performed using \u201cIBM SPSS version 29.0\u201d. The serum SIRT1 level was determined by the ELISA method. Results: We found that rs3818292 was associated with increased odds of developing MS under the dominant (p = 0.007) and allelic genetic (p = 0.004) models. rs3758391 was associated with increased odds of developing under the co-dominant (p &lt; 0.001), overdominant (p &lt; 0.001), dominant (p &lt; 0.001), and allelic (p = 0.002) genetic models. rs7895833 was associated with increased odds of developing MS under co-dominant (p &lt; 0.001), overdominant (p &lt; 0.001), dominant (p &lt; 0.001), and allelic (p &lt; 0.001) genetic models. Additional sex-differentiated analysis within females revealed that the rs3758391 was associated with an increased odds ratio for the occurrence of MS among the co-dominant (p = 0.006), dominant (p = 0.002), and allelic (p = 0.001). rs7895833 was associated with an increased odds ratio for the development of MS under the co-dominant (p &lt; 0.001), overdominant (p &lt; 0.001), dominant (p &lt; 0.001), and allelic (p &lt; 0.001) genetic models. Age-differentiated analysis showed that rs3758391 was associated with an increased odds ratio for the development of MS in younger patients under the codominant (p = 0.002), overdominant (p = 0.003), and dominant (p = 0.004) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the overdominant genetic model (p = 0.013). In elderly patients, rs3818292 was associated with an increased odds ratio for the occurrence of MS under the dominant (p = 0.008) and allelic (p = 0.009) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the codominant (p = 0.011 and p = 0.012), dominant (p = 0.001), and allelic (p &lt; 0.001) genetic models. We also found that serum SIRT1 levels were statistically significantly different between MS patients and control group subjects (p &lt; 0.001). In addition, comparison of SIRT1 levels between study groups and genotypes showed that rs3818292 AA (p = 0.001), rs3758391 CT (p &lt; 0.001), and rs7895833 AA (p = 0.002) and AG (p = 0.004) had higher SIRT1 levels in the control group than in the MS group. All results were provided after strict Bonferroni correction. Conclusions: Genetic variations in SIRT1 rs3818292, rs3758391, and rs7895833 are associated with multiple sclerosis, with possible differences in gender and age, as well as lower serum SIRT1 levels.<\/jats:p>","DOI":"10.3390\/diagnostics13203287","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T10:32:24Z","timestamp":1698057144000},"page":"3287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of SIRT1 Gene Polymorphisms and Serum Levels in Patients with Multiple Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3419-8997","authenticated-orcid":false,"given":"Kriste","family":"Kaikaryte","sequence":"first","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-8825","authenticated-orcid":false,"given":"Greta","family":"Gedvilaite","sequence":"additional","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Balnyte","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrida","family":"Uloziene","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasa","family":"Liutkeviciene","sequence":"additional","affiliation":[{"name":"Laboratory of Ophthalmology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania"},{"name":"Department of Ophthalmology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2 Str., 50161 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/B978-0-444-64076-5.00046-6","article-title":"Multiple sclerosis","volume":"148","author":"Cotsapas","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00281-021-00907-3","article-title":"Genetics and functional genomics of multiple sclerosis","volume":"44","author":"Kim","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1586\/14737175.2013.865866","article-title":"Environmental factors in multiple sclerosis","volume":"13","author":"Ascherio","year":"2013","journal-title":"Expert Rev. Neurother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1136\/jnnp.2011.240432","article-title":"Latitude is significantly associated with the prevalence of multiple sclerosis: A meta-analysis","volume":"82","author":"Simpson","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e01150","DOI":"10.1002\/brb3.1150","article-title":"Incidence rate and sex ratio in multiple sclerosis in Lithuania","volume":"9","author":"Valadkeviciene","year":"2019","journal-title":"Brain Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"831168","DOI":"10.3389\/fimmu.2022.831168","article-title":"Regulation of SIRT1 and Its Roles in Inflammation","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1167\/iovs.08-2817","article-title":"Sirt1 involvement in rd10 mouse retinal degeneration","volume":"50","author":"Jaliffa","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chojdak-\u0141ukasiewicz, J., Bizo\u0144, A., Waliszewska-Pros\u00f3\u0142, M., Piwowar, A., Budrewicz, S., and Pokryszko-Dragan, A. (2022). Role of Sirtuins in Physiology and Diseases of the Central Nervous System. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102434"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1523\/JNEUROSCI.3442-11.2012","article-title":"SIRT1 protects against \u03b1-synuclein aggregation by activating molecular chaperones","volume":"32","author":"Donmez","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/gerona\/glx028","article-title":"Physical Resilience: Opportunities and Challenges in Translation","volume":"72","author":"LeBrasseur","year":"2017","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"778","DOI":"10.3389\/fnins.2018.00778","article-title":"Sirtuins in Neuroendocrine Regulation and Neurological Diseases","volume":"12","author":"Fujita","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.2174\/1871530321666210309112234","article-title":"Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions","volume":"21","author":"Sharma","year":"2021","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.msard.2019.06.004","article-title":"Sirtuins in Multiple Sclerosis: The crossroad of neurodegeneration, autoimmunity and metabolism","volume":"34","author":"Foolad","year":"2019","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Piacente, F., Bottero, M., Benzi, A., Vigo, T., Uccelli, A., Bruzzone, S., and Ferrara, G. (2022). Neuroprotective Potential of Dendritic Cells and Sirtuins in Multiple Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084352"},{"key":"ref_16","first-page":"179","article-title":"The emerging role of Nrf2 in mitochondrial function","volume":"88 Pt B","author":"Abramov","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1212\/WNL.0000000000002035","article-title":"Alzheimer\u2019s Disease Cooperative Study A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease","volume":"85","author":"Turner","year":"2015","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s10020-021-00279-2","article-title":"Novel targeted therapies for Parkinson\u2019s disease","volume":"27","author":"Ntetsika","year":"2021","journal-title":"Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41419-018-0799-z","article-title":"A novel small-molecule activator of Sirtuin-1 induces autophagic cell death\/mitophagy as a potential therapeutic strategy in glioblastoma","volume":"9","author":"Yao","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/ncb2735","article-title":"Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain","volume":"15","author":"Rafalski","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"779177","DOI":"10.3389\/fimmu.2021.779177","article-title":"SIRT1: A Potential Therapeutic Target in Autoimmune Diseases","volume":"12","author":"Shen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_22","unstructured":"(2023, March 22). RS3818292 Refsnp Report\u2014dbSNP\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs3818292."},{"key":"ref_23","unstructured":"(2023, March 22). RS3758391 RefSNP Report\u2014dbSNP\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs3758391#frequency_tab."},{"key":"ref_24","unstructured":"(2023, March 22). RS7895833 Refsnp Report\u2014dbSNP\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs7895833."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S1474-4422(15)00393-2","article-title":"MAGNIMS Study Group MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines","volume":"15","author":"Filippi","year":"2016","journal-title":"Lancet. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lin, H., Hargreaves, K.A., Li, R., Reiter, J.L., Wang, Y., Mort, M., Cooper, D.N., Zhou, Y., Zhang, C., and Eadon, M.T. (2019). RegSNPs-intron: A computational framework for predicting pathogenic impact of intronic single nucleotide variants. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1847-4"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/ane.12433","article-title":"Hormonal and gender-related immune changes in multiple sclerosis","volume":"132","author":"Airas","year":"2015","journal-title":"Acta Neurol. Scand."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1093\/brain\/awg081","article-title":"Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process","volume":"126","author":"Confavreux","year":"2003","journal-title":"Brain A J. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0074-7742(07)79019-0","article-title":"Prognostic factors in multiple sclerosis","volume":"79","author":"Bergamaschi","year":"2007","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/imm.13004","article-title":"Impact of sex hormones on immune function and multiple sclerosis development","volume":"156","author":"Ysrraelit","year":"2019","journal-title":"Immunology"},{"key":"ref_32","first-page":"1","article-title":"Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy","volume":"19","author":"Ghasemi","year":"2017","journal-title":"Cell J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kritsilis, M., V Rizou, S., Koutsoudaki, P.N., Evangelou, K., Gorgoulis, V.G., and Papadopoulos, D. (2018). Ageing, Cellular Senescence and Neurodegenerative Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102937"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1212\/WNL.0b013e318230a17d","article-title":"Age and disability accumulation in multiple sclerosis","volume":"77","author":"Scalfari","year":"2011","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1474-4422(22)00184-3","article-title":"Ageing and multiple sclerosis","volume":"22","author":"Graves","year":"2023","journal-title":"Lancet. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10677","DOI":"10.1038\/s41598-021-90059-z","article-title":"Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson\u2019s disease","volume":"11","author":"Boros","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/ene.12255","article-title":"Multiple sclerosis and risk of Parkinson\u2019s disease: A Danish nationwide cohort study","volume":"21","author":"Nielsen","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"171871","DOI":"10.1098\/rsos.171871","article-title":"Correlations between SIRT1 gene polymorphisms and diabetic kidney disease","volume":"5","author":"Yue","year":"2018","journal-title":"R. Soc. Open Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e31959","DOI":"10.1097\/MD.0000000000031959","article-title":"Renal diseases associated with multiple sclerosis: A narrative review","volume":"101","author":"Alugba","year":"2022","journal-title":"Medicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00439-008-0567-8","article-title":"Association of SIRT1 gene variation with visceral obesity","volume":"124","author":"Peeters","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.29245\/2572.942X\/2016\/7.1064","article-title":"Obesity and Multiple Sclerosis Susceptibility: A Review","volume":"1","author":"Gianfrancesco","year":"2016","journal-title":"J. Neurol. Neuromed."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/ahg.12363","article-title":"Type 2 diabetes-associated polymorphisms correlate with SIRT1 and TGF-\u03b21 gene expression","volume":"84","author":"Ortega","year":"2020","journal-title":"Ann. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kilic, U., Gok, O., Erenberk, U., Dundaroz, M.R., Torun, E., Kucukardali, Y., Elibol-Can, B., Uysal, O., and Dundar, T. (2015). A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117954"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.regg.2019.01.008","article-title":"Polymorphism rs7895833 in the SIRT1 gene and its association with dyslipidaemia in the elderly","volume":"54","author":"Casarotto","year":"2019","journal-title":"Rev. Espa\u00f1ola Geriatr\u00eda Gerontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1194\/jlr.R300019-JLR200","article-title":"Effects of infection and inflammation on lipid and lipoprotein metabolism: Mechanisms and consequences to the host","volume":"45","author":"Khovidhunkit","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_46","first-page":"339","article-title":"Sirtuin 1 gene polymorphisms are associated with body fat and blood pressure in Japanese","volume":"157","author":"Shimoyama","year":"2011","journal-title":"Transl. Res. J. Lab. Clin. Med."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/20\/3287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:24Z","timestamp":1760130624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/20\/3287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":46,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["diagnostics13203287"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13203287","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}