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

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 "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 (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. 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.

Association of STAT4 Gene Polymorphisms (rs10181656, rs7574865, rs7601754, rs10168266) and Serum STAT4 Levels in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a progressive degenerative disease that affects the central part of the retina: the macula. AMD is the most common cause of central vision loss in industrialized countries. Increasing attention is being paid to the study of genetic factors that may influence the manifestation of AMD. STAT4 protein is involved in the pathogenesis of numerous inflammatory processes, so we decided to investigate the association between STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) and age-related macular degeneration. PURPOSE: To investigate the association between STAT4 (rs10181656, rs7574865, rs7601754, and rs10168266) gene polymorphisms and STAT4 serum levels in patients with age-related macular degeneration. METHODS AND PARTICIPANTS: The study included 150 individuals with early AMD, 150 individuals with exudative AMD, and 200 healthy subjects. DNA was extracted from peripheral blood leukocytes using the DNA salting-out method, and the genotyping was performed using a real-time polymerase chain reaction (RT-PCR) method. STAT4 serum levels were evaluated using the ELISA method. Statistical analysis was performed using "IBM SPSS "Statistics 29.0" software". RESULTS: The study revealed no statistically significant differences in the distribution of genotypes and alleles for the STAT4 polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) between patients with AMD and the control group. Similarly, a gender-based analysis did not yield any significant differences in the genotype or allele frequencies. Age group comparisons also showed no statistically significant variations in the presence of these STAT4 polymorphisms between AMD patients and the control group. However, notably, individuals with exudative AMD displayed lower levels of serum STAT4 in comparison to the control group (median (IQR): 0.118 (0.042) vs. 0.262 (0.385), p = 0.005). CONCLUSION: Investigating STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) did not reveal a significant association with AMD. However, further analysis demonstrated intriguing findings regarding serum STAT4 levels. Exudative AMD patients with at least one G allele of the STAT4 rs10181656 exhibited significantly lower serum STAT4 levels than the control group subjects (p = 0.011). Similarly, those with at least one T allele of STAT4 rs10168266 had lower serum STAT4 levels compared to the control group subjects (p = 0.039). These results suggest a potential link between specific STAT4 genotypes and serum STAT4 levels in exudative AMD patients, shedding light on a novel aspect of the disease.

IL-10 Gene Polymorphisms and IL-10 Serum Levels in Patients with Multiple Sclerosis in Lithuania.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with features of demyelination and axonal degeneration at a young age. Genetic factors may play an important role in the development of multiple sclerosis. (1) Objective: To investigate IL-10 rs1800871, rs1800872, rs1800896, and IL-10 serum levels in patients with multiple sclerosis. (2) Methods: Our study included patients with multiple sclerosis (n = 127) and healthy volunteers (n = 195). The subjects' DNA was extracted from peripheral blood leukocytes and genotyped by real-time polymerase chain reaction. The results were analyzed using the program "IBM SPSS Statistics 27.0". (3) Results: The IL-10 SNPs were analyzed between the MS and control groups; however, no statistically significant results were found. The serum levels of IL-10 in the groups of MS and healthy subjects were not statistically significantly different (median (IQR): 0.828 (1.533) vs. 0.756 (0.528), p = 0.872). (4) Conclusions: IL-10 rs1800871, rs1800872, and rs1800896 and serum IL-10 levels are not likely to be associated with MS development. However, individuals carrying the rare haplotypes of rs1800871, rs1800872, and rs1800896 were associated with increased odds of MS (p = 0.006).

SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration.

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels.

Value of Serum Sirtuin-1 (SIRT1) Levels and SIRT1 Gene Variants in Periodontitis Patients.

Background and Objectives: Periodontitis is a multifactorial inflammatory disease associated with biofilm dysbiosis and is defined by progressive periodontium destruction. Genes largely regulate this entire process. SIRTs are a group of histone deacetylases (HDACs) intimately involved in cell metabolism and are responsible for altering and regulating numerous cell functions. Understanding SIRTs and their functions in periodontitis may be useful for therapeutic treatment strategies in the future. The aim of our study was to investigate the associations amid SIRT1 single-gene nucleotide polymorphisms (rs3818292, rs3758391, and rs7895833) and SIRT1 serum levels for patients affected by periodontitis in the Caucasian population. Materials and Methods: The study included 201 patients affected by periodontitis and 500 healthy controls. DNA extraction from peripheral leukocytes was carried out using commercial kits. The real-time PCR method was selected for the determination of the genotype of the periodontitis patients and the control group. The ELISA method was used to measure the SIRT1 concentration. A statistical data analysis was performed using "BM SPSS Statistics 27.0" software. Results: The SIRT1 rs3818292 AG genotype was associated with a 2-fold and 1.9-fold increase in the development of periodontitis under the codominant and overdominant models (OR = 1.959; CI = 1.239-3.098; p = 0.004; and OR = 1.944; CI = 1.230-3.073; p = 0.004, respectively). The serum SIRT1 levels were not statistically significantly different between subjects in the periodontitis and control groups (0.984 (5.159) ng/mL vs. 0.514 (7.705) ng/mL, p = 0.792). Conclusions: in our study, the genotypes and alleles of SIRT1 rs3818292, rs3758391, and rs7895833 statistically significantly differed between the periodontitis and control groups, exclusively in the male population and subjects older than 60 years.

Haplotypes of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 Gene Polymorphisms in Age-Related Macular Degeneration.

BACKGROUND: To determine the impact of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 genotypes on the development of age-related macular degeneration (AMD) in the Lithuanian population. METHODS: A total of 916 subjects were examined: 309 patients with early AMD, 301 patients with exudative AMD, and 306 healthy controls. The genotyping of HTRA1 rs11200638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 was carried out using the RT-PCR method. RESULTS: Our study showed that single-nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative AMD, and the variant in KCTD10 (rs56209061) was found to be associated with decreased odds of early and exudative AMD development after adjustments for age and gender in early AMD analysis and after adjustments only for age in exudative AMD. The haplotype containing two minor alleles C-A and the G-A haplotype in rs3793784-rs11200638 were statistically significantly associated with an increased risk of exudative AMD development after adjustment for age, while the G-G haplotype showed a protective role against early and exudative AMD and the haplotype C-G in rs3793784-rs11200638 was associated with a decreased risk only of exudative AMD development. CONCLUSIONS: Our study identified two markers, rs11200638 and rs3793784, as risk factors for early and exudative AMD, and one marker, rs56209061, as a protective factor for early and exudative AMD development. The haplotypes constructed of rs3793784-rs11200638 were found to be associated with AMD development, as well.