Role of SIRT1 Gene Polymorphisms and Serum Levels in Patients with Multiple Sclerosis

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.

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.

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 < 0.001), overdominant (p < 0.001), dominant (p < 0.001), and allelic (p = 0.002) genetic models. rs7895833 was associated with increased odds of developing MS under co-dominant (p < 0.001), overdominant (p < 0.001), dominant (p < 0.001), and allelic (p < 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 < 0.001), overdominant (p < 0.001), dominant (p < 0.001), and allelic (p < 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 < 0.001) genetic models. We also found that serum SIRT1 levels were statistically significantly different between MS patients and control group subjects (p < 0.001). In addition, comparison of SIRT1 levels between study groups and genotypes showed that rs3818292 AA (p = 0.001), rs3758391 CT (p < 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.

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.