Kaikaryte Kriste, Gedvilaite Greta, Balnyte Renata, Uloziene Ingrida, Liutkeviciene Rasa
Laboratory of Ophthalmology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania.
Department of Neurology, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania.
Diagnostics (Basel). 2023 Oct 23;13(20):3287. doi: 10.3390/diagnostics13203287.
The purpose of this work was to investigate the prevalence of 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 ( = 0.007) and allelic genetic ( = 0.004) models. rs3758391 was associated with increased odds of developing under the co-dominant ( < 0.001), overdominant ( < 0.001), dominant ( < 0.001), and allelic ( = 0.002) genetic models. rs7895833 was associated with increased odds of developing MS under co-dominant ( < 0.001), overdominant ( < 0.001), dominant ( < 0.001), and allelic ( < 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 ( = 0.006), dominant ( = 0.002), and allelic ( = 0.001). rs7895833 was associated with an increased odds ratio for the development of MS under the co-dominant ( < 0.001), overdominant ( < 0.001), dominant ( < 0.001), and allelic ( < 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 ( = 0.002), overdominant ( = 0.003), and dominant ( = 0.004) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the overdominant genetic model ( = 0.013). In elderly patients, rs3818292 was associated with an increased odds ratio for the occurrence of MS under the dominant ( = 0.008) and allelic ( = 0.009) genetic models. rs7895833 was associated with an increased odds ratio for the occurrence of MS under the codominant ( = 0.011 and = 0.012), dominant ( = 0.001), and allelic ( < 0.001) genetic models. We also found that serum SIRT1 levels were statistically significantly different between MS patients and control group subjects ( < 0.001). In addition, comparison of SIRT1 levels between study groups and genotypes showed that rs3818292 AA ( = 0.001), rs3758391 CT ( < 0.001), and rs7895833 AA ( = 0.002) and AG ( = 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 rs3818292, rs3758391, and rs7895833 are associated with multiple sclerosis, with possible differences in gender and age, as well as lower serum SIRT1 levels.
本研究旨在调查立陶宛人群中与多发性硬化症（MS）相关的rs3818292、rs3758391和rs7895833单核苷酸多态性的患病率以及SIRT1血清水平。
本研究共纳入250例MS患者和250名健康对照。采用RT-PCR方法进行基因分型。使用“IBM SPSS 29.0版”进行统计分析。通过ELISA方法测定血清SIRT1水平。
我们发现，在显性（P = 0.007）和等位基因遗传（P = 0.004）模型下，rs3818292与患MS的几率增加相关。在共显性（P < 0.001）、超显性（P < 0.001）、显性（P < 0.001）和等位基因（P = 0.002）遗传模型下，rs3758391与患MS的几率增加相关。在共显性（P < 0.001）、超显性（P < 0.001）、显性（P < 0.001）和等位基因（P < 0.001）遗传模型下，rs7895833与患MS的几率增加相关。在女性中进行的额外性别差异分析显示，在共显性（P = 0.006）、显性（P = 0.002）和等位基因（P = 0.001）模型下，rs3758391与MS发生几率增加相关。在共显性（P < 0.001）、超显性（P < 0.001）、显性（P < 0.001）和等位基因（P < 0.001）遗传模型下，rs7895833与MS发生几率增加相关。年龄差异分析显示，在共显性（P = 0.002）、超显性（P = 0.003）和显性（P = 0.004）遗传模型下，rs3758391与年轻患者患MS的几率增加相关。在超显性遗传模型下（P = 0.013），rs7895833与MS发生几率增加相关。在老年患者中，在显性（P = 0.008）和等位基因（P = 0.009）遗传模型下，rs3818292与MS发生几率增加相关。在共显性（P = 0.011和P = 0.012）、显性（P = 0.001）和等位基因（P < 0.001）遗传模型下，rs7895833与MS发生几率增加相关。我们还发现，MS患者与对照组受试者之间的血清SIRT1水平在统计学上有显著差异（P < 0.001）。此外，研究组与基因型之间SIRT1水平的比较显示，rs3818292 AA（P = 0.001）、rs3758391 CT（P < 0.001）以及rs7895833 AA（P = 0.002）和AG（P = 0.004）在对照组中的SIRT1水平高于MS组。所有结果均经过严格的Bonferroni校正后提供。
rs3818292、rs3758391和rs7895833的基因变异与多发性硬化症相关，在性别和年龄上可能存在差异，且血清SIRT1水平较低。
