Role of <i>SIRT1</i> Gene Polymorphisms and Serum Levels in Patients with Multiple Sclerosis

Aim: The purpose of this work was to investigate the prevalence of <i>SIRT1</i> 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 “IBM SPSS version 29.0”. 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 (<i>p</i> = 0.007) and allelic genetic (<i>p</i> = 0.004) models. rs3758391 was associated with increased odds of developing under the co-dominant (<i>p</i> < 0.001), overdominant (<i>p</i> < 0.001), dominant (<i>p</i> < 0.001), and allelic (<i>p</i> = 0.002) genetic models. rs7895833 was associated with increased odds of developing MS under co-dominant (<i>p</i> < 0.001), overdominant (<i>p</i> < 0.001), dominant (<i>p</i> < 0.001), and allelic (<i>p</i> < 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 (<i>p</i> = 0.006), dominant (<i>p</i> = 0.002), and allelic (<i>p</i> = 0.001). rs7895833 was associated with an increased odds ratio for the development of MS under the co-dominant (<i>p</i> < 0.001), overdominant (<i>p</i> < 0.001), dominant (<i>p</i> < 0.001), and allelic (<i>p</i> < 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 (<i>p</i> = 0.002), overdominant (<i>p</i> = 0.003), and dominant (<i>p</i> = 0.004) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the overdominant genetic model (<i>p</i> = 0.013). In elderly patients, rs3818292 was associated with an increased odds ratio for the occurrence of MS under the dominant (<i>p</i> = 0.008) and allelic (<i>p</i> = 0.009) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the codominant (<i>p</i> = 0.011 and <i>p</i> = 0.012), dominant (<i>p</i> = 0.001), and allelic (<i>p</i> < 0.001) genetic models. We also found that serum SIRT1 levels were statistically significantly different between MS patients and control group subjects (<i>p</i> < 0.001). In addition, comparison of SIRT1 levels between study groups and genotypes showed that rs3818292 AA (<i>p</i> = 0.001), rs3758391 CT (<i>p</i> < 0.001), and rs7895833 AA (<i>p</i> = 0.002) and AG (<i>p</i> = 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 <i>SIRT1</i> rs3818292, rs3758391, and rs7895833 are associated with multiple sclerosis, with possible differences in gender and age, as well as lower serum SIRT1 levels.