Associations between ZNF676, CTC1 Gene Polymorphisms and Relative Leukocyte Telomere Length with Myopia and Its Degree.

BACKGROUND: The interaction between environmental and genetic factors that influence eye growth, regulated by vision, contributes to the development and progression of myopia. This dynamic interaction significantly contributes to the multifaceted development and progression of myopia, a prevalent ocular condition. Our study delves into the associations between ZNF676 and CTC1 gene polymorphisms and their impact on the relative leukocyte telomere length (relative LTL) in myopia, as well as its degree. By unravelling these underpinnings in conjunction with environmental influences, we aim to enhance our understanding of the complex mechanisms that drive the onset and severity of myopia. METHODS: This study included patients with myopia and ophthalmologically healthy subjects. DNA was extracted from peripheral venous blood by the salting out method. Genotyping of ZNF676 rs412658 and CTC1 rs3027234, as well as the measurement of relative LTL, were conducted using a real-time polymerase chain reaction method (RT-PCR). The data obtained were statistically analyzed using the "IBM SPSS Statistics 29.0" software program. RESULTS: The results show that myopic patients who are homozygous for the rs3027234 rare allele genotype of the CTC1 gene have statistically significantly shorter relative LTL compared to patients with the CC and CT genotypes. Also, men with the CTC1 rs3027234 TT genotype have statistically significantly longer leukocyte telomeres than women with the same genotype. The respective median (IQR) of the relative LTL for women and men is 0.280 (0.463) vs. 0.696 (0.440), with a p-value of 0.027. The myopia group with the ZNF676 rs412658 CC genotype has statistically significantly shorter leukocyte telomeres than the control group with the same genotype (age ≤ 29), and the p-value is 0.011. Also, the myopia group with the ZNF676 rs412658 CT and CTC1 rs3027234 CT genotypes have statistically significantly longer leukocyte telomeres than the control group with the same genotypes (age > 29), with p-values that are, respectively, 0.016 and 0.012. The evaluation of the genotype distributions of the polymorphisms in the myopia patients showed that ZNF676 rs412658 CT genotype carriers have 4-fold decreased odds of high myopia occurrence (OR = 0.250; CI: 0.076-0.826; p = 0.023). Also, the evaluation of the allele distributions of the polymorphism under the additive genetic model in the myopia group showed that the ZNF676 rs412658 T allele was associated with similar odds of high myopia (OR = 0.269; 95% CI: 0.090-0.807; p = 0.019). The comprehensive p-value, assessing the relative LTL of subjects across the different levels of myopia, signifies a statistical difference in the relative LTL among individuals with varying degrees of myopia. There was a statistically significant difference in relative LTL between mild and moderate myopia degrees (0.819 (1.983) vs. 0.083 (0.930), p = 0.007). CONCLUSIONS: CTC1 rs3027234 TT may be considered a protective genotype for telomere shortening in men, while the overall telomere shortening might be linked to the worse myopia degree. The ZNF676 rs412658 T allele may protect against a high myopia occurrence.

The role of SIRT1 level and SIRT1 gene polymorphisms in optic neuritis patients with multiple sclerosis.

THE AIM: To investigate the role of Sirtuin 1 (SIRT1) level and SIRT1 (rs3818292, rs3758391, rs7895833) gene polymorphisms in patients with optic neuritis (ON) and multiple sclerosis (MS). METHODS: 79 patients with ON and 225 healthy subjects were included in the study. ON patients were divided into 2 subgroups: patients with MS (n = 30) and patients without MS (n = 43). 6 ON patients did not have sufficient data for MS diagnosis and were excluded from the subgroup analysis. DNA was extracted from peripheral blood leukocytes and genotyped by real-time polymerase chain reaction. Results were analysed using the program "IBM SPSS Statistics 27.0". RESULTS: We discovered that SIRT1 rs3758391 was associated with a twofold increased odds of developing ON under the codominant (p = 0.007), dominant (p = 0.011), and over-dominant (p = 0.008) models. Also, it was associated with a threefold increased odds ofON with MS development under the dominant (p = 0.010), twofold increased odds under the over-dominant (p = 0.032) models and a 1.2-fold increased odds of ON with MS development (p = 0.015) under the additive model. We also discovered that the SIRT1 rs7895833 was significantly associated with a 2.5-fold increased odds of ON development under the codominant (p = 0.001), dominant (p = 0.006), and over-dominant (p < 0.001) models, and a fourfold increased odds of ON with MS development under the codominant (p < 0.001), dominant (p = 0.001), over-dominant (p < 0.001) models and with a twofold increased odds of ON with MS development (p = 0.013) under the additive genetic model. There was no association between SIRT1 levels and ON with/without MS development. CONCLUSIONS: SIRT1 rs3758391 and rs7895833 polymorphisms are associated with ON and ON with MS development.

The survival rate of laryngeal squamous cell carcinoma: impact of IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532 single nucleotide polymorphisms.

PURPOSE: Results of laryngeal squamous cell carcinoma (LSCC) treatment and the 5 year survival rate of these patients remain poor. To purify therapeutic targets, investigation of new specific and prognostic blood-based markers for LSCC development is essential. METHODS: In the present study, we evaluated five single nucleotide polymorphisms (SNPs): IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532, and determined their associations with the patients' 5 year survival rate. Also, we performed a detailed statistical analysis of different LSCC patients' characteristics impact on their survival rate. RESULTS: Three hundred fifty-three LSCC patients and 538 control subjects were included in this study. The multivariable Cox regression analysis revealed a significant association between patients' survival rate and distribution of IL1RAP rs4624606 variants: patients carrying AT genotype at IL1RAP rs4624606 had a lower risk of death (p = 0.044). Also, it was revealed that tumor size (T) (p = 0.000), tumor differentiation grade (G) (p = 0.015), and IL1RAP rs4624606 genotype (p = 0.044) were effective variables in multivariable Cox regression analysis prognosing survival of LSCC patients. The specific-LSCC 5 year survival rate was 77%. CONCLUSIONS: In summary, our findings indicate that the genotypic distribution of IL1RAP rs4624606 influences the 5 year survival rate of LSCC patients. The results of the present study facilitate a more complete understanding of LSCC at the biological level, thus providing the base for the identification of new specific and prognostic blood-based markers for LSCC development.

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration.

Telomere shortening is well known to be associated with ageing. Age is the most decisive risk factor for age-related macular degeneration (AMD) development. The older the individual, the higher the AMD risk. For this reason, we aimed to find any associations between telomere length, distribution of genetic variants in telomere-related genes (TERT, TERT-CLPTM1, TRF1, TRF2, and TNKS2), and serum TERF-1 and TERF2 levels on AMD development. METHODS: Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA). RESULTS: We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group. CONCLUSIONS: In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.

Association of APOE Serum Levels and APOE ε2, ε3, and ε4 Alleles with Optic Neuritis.

Optical neuritis (ON), otherwise known as optical nerve damage, is a term used to describe various environmental and body conditions that lead to optic nerve dysfunction. Neurologists are well aware of conditions that cause optic neuropathy, such as trauma, infections, malnutrition, and various toxins. As optic neuritis is a multifactorial demyelinating or infectious process, genetic predisposition may also influence the progression of optic neuritis. This study aimed to evaluate the association of ON (with and without multiple sclerosis) with APOE alleles and APOE serum levels. We found that the APOE ε3/ε3 genotype was statistically less common in the ON group of males than in the control group (p = 0.045). Moreover, the APOE ε3/ε3 genotype had a 3.7-fold increase in the odds of ON development in males (OR = 3.698; CI: 1.503-9.095; p = 0.004). In contrast, the APOE ε3/ε4 genotype had a 4.1-fold decrease in the odds of ON development in males (OR = 0.242; CI: 0.083-0.704; p = 0.009). APOE serum levels were statistically significantly higher in the ON group than in the control group (p = 0.042). The APOE ε3/ε3 genotype may increase males' risk of developing ON, while the ε3/ε4 genotype may reduce males' risk of developing ON.

The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma.

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients' five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.

Molecular Markers of Telomerase Complex for Patients with Pituitary Adenoma.

Pituitary adenoma (PA) is the most common benign tumor of the pituitary gland. The pathogenesis of most PA is considered as a multifactorial process, that involves genetic mutations, alterations in gene transcription, and epigenetic factors. Their interaction promotes tumorigenesis. The processes are increasingly focused on changes in telomere length. Our study enrolled 126 patients with PA and 368 healthy subjects. DNA samples from peripheral blood leukocytes were purified by the DNA salting-out method. The RT-PCR carried out SNPs and relative leukocyte telomere lengths (RLTL). ELISA determined the level of TEP1 in blood serum. Binary logistic regression revealed that TERC rs35073794 is likely associated with increased odds of PA development and macro-PA development. It is also associated with decreased odds of active PA, non-invasive PA, and PA without relapse development. Also, we discovered that PA patients with at least one G allele of the TEP1 gene polymorphism rs1713418 have lower serum TEP1 levels than healthy individuals (p = 0.035). To conclude, the study revealed that TERC rs35073794 might be a potential biomarker for PA development.

Associations of Tumor Necrosis Factor-Alpha Gene Polymorphisms (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-Alpha Serum Concentration with Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a neurodegenerative disease leading to irreversible central vision loss among the elderly in developed countries. While the disease accounts for 9% of all cases of vision loss, the prevalence of AMD is likely to increase due to the exponential aging of the population. Due to this reason, our study aimed to determine the associations of tumor necrosis factor-alpha (TNF-α) gene single-nucleotide polymorphisms (SNPs) TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-α serum concentration with age-related macular degeneration. Analysis of TNF-α rs1800630, rs1800629, and rs361525 polymorphisms showed that the TNF-α rs1800630 A allele was statistically significantly more frequent in the exudative AMD group compared to the control group (p = 0.029). Additionally, the TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in the control group of healthy females (p = 0.027). The TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in females with early AMD (p = 0.014). TNF-α rs1800630, rs1800629, and rs361525 haplotype A-A-G were associated with decreased odds of exudative AMD (p < 0.0001), and haplotype A-G-G was associated with 24-fold increased exudative AMD occurrence (p < 0.0001). TNF-α protein levels were lower in subjects with exudative AMD compared to the control group (p < 0.001). The study showed significant associations between inflammatory cytokine TNF-α single-nucleotide polymorphisms and serum level with AMD pathogenesis. Analysis of TNF-α genotypes and serum concentration may be helpful for the AMD diagnosis.

CCL2, CCR2 Gene Variants and CCL2, CCR2 Serum Levels Association with Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of progressive and irreversible blindness in developed countries. Although the pathogenesis is not fully understood, AMD is a multifactorial pathology with an accumulation of inflammatory components and macrophages and a strong genetic predisposition. Our purpose was to investigate the association between early AMD and CCL2 (rs1024611, rs4586, rs2857656) and CCR2 (rs1799865) single nucleotide polymorphisms (SNPs) and CCL2, CCR2 serum levels in a Lithuanian population. METHODS: The study included 310 patients with early AMD and 384 healthy subjects. Genotyping of CCL2 rs1024611, rs4586, rs2857656, and CCR2 rs1799865 was performed using a real-time polymerase chain reaction method, while CCL2 and CCR2 chemokines serum concentrations were analyzed using an enzyme-linked immunosorbent assay. RESULTS: We found that the G allele at CCL2 rs1024611 was more prevalent in the early AMD group than in controls (29.2% vs. 24.1%, p = 0.032). Similarly, the C allele in CCL2 rs2857656 is more common in the early AMD group than in controls (29.2% vs. 24.2%, p = 0.037). Binomial logistic regression revealed that each G allele in rs1024611 was associated with 1.3-fold increased odds of developing early AMD under the additive model (OR = 1.322; 95% CI: 1.032-1.697, p = 0.027) as was each C allele in rs2857656 under the additive model (OR = 1.314; 95% CI: 1.025-1.684, p = 0.031). Haplotype analysis revealed that the C-A-G haplotype of CCL2 SNPs was associated with 35% decreased odds of early AMD development. Further analysis showed elevated CCL2 serum levels in the group with early AMD compared to controls (median (IQR): 1181.6 (522.6) pg/mL vs. 879.9 (494.4) pg/mL, p = 0.013); however, there were no differences between CCR2 serum levels within groups. CONCLUSIONS: We found the associations between minor alleles at CCL2 rs1024611 and rs2857656, elevated CCL2 serum levels, and early AMD development.

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.

VEGFA Haplotype and VEGF-A and VEGF-R2 Protein Associations with Exudative Age-Related Macular Degeneration.

Our study aimed to reveal the associations between VEGFA SNPs (rs1570360, rs699947, rs3025033, and rs2146323), their haplotypes, VEGF-A and VEGF-R2 serum concentrations, and early and exudative AMD. A total of 339 subjects with early AMD and 419 with exudative AMD groups, and 374 healthy subjects, were genotyped for four VEGFA SNPs (rs1570360, rs699947, rs3025033, and rs2146323). VEGF-A and VEGFR-2 serum concentrations were measured in exudative AMD and controls. The results revealed that rs3025033 G allele was significantly associated with lower odds of exudative AMD under the dominant model (OR = 0.67; 95% CI: 0.49-0.80; p = 0.0088) and additive (OR = 0.7; 95% CI: 0.54-0.90; p = 0.0058) models after Bonferroni correction. In the female group, rs3025033 AG genotype was associated with exudative AMD under the codominant model (OR = 0.57; 95% CI: 0.37-0.87; p = 0.009) and G allele under the dominant (OR = 0.55; 95% CI: 0.37-0.82; p = 0.0032) and additive models (OR = 0.60; 95% CI: 0.42-0.84; p = 0.0028). Haplotype analysis revealed that individuals carrying rs1570360, rs699947, rs3025033, and rs2146323 haplotype A-A-G-A had decreased risk of exudative AMD (OR = 0.46, 95% CI: 0.23-0.90; p = 0.023). The VEGF-A and VEGF-R2 serum concentrations did not differ between study groups; we found that patients with exudative AMD carrying at least one C allele at rs699947 have statistically significantly higher VEGF-A serum concentrations compared to AA genotype carriers (485.95 (945.93) vs. 194.97 (-), respectively, p = 0.046). In conclusion, we found that VEGFA rs3025033 and haplotype rs1570360A-rs699947A-rs3025033G- rs2146323A play a protective role for exudative AMD in the Caucasian population. Furthermore, rs699947 is associated with elevated VEGF-A serum concentrations in exudative AMD.

Circulating hsa-let-7e-5p and hsa-miR-125a-5p as Possible Biomarkers in the Diagnosis of Major Depression and Bipolar Disorders.

BACKGROUND: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders. METHODS: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires. RESULTS: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%. CONCLUSIONS: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD.

Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate.

BACKGROUND: SIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified. OBJECTIVES: The study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: The study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method. RESULTS: Our study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR = 1.960 95% CI = 1.028-3.737; p= 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR = 2.387 95% CI = 1.091-5.222; p= 0.029 and OR = 2.287 95% CI = 1.070-4.888; p= 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls (p= 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found. CONCLUSION: The present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.

RP1L1 rs3924612 gene polymorphism and RP1L1 protein associations among patients with early age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is one of the most common causes of blindness in developed world countries. It mainly affects the elderly. The incidence of the disease is only slightly below that of cancer and cardiovascular diseases. This study aimed to determine the association of RP1L1 single nucleotide polymorphism and serum RP1L1 levels with the onset of the early AMD. AIM: The aim of this study was to determine the association of RP1L1 single nucleotide polymorphism with the onset of the early age-related macular degeneration (AMD). METHODS: The study examined 615 subjects: 309 with a diagnosis of the early AMD and 306 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by the DNA salting-out method. Genotyping was carried out by the real-time polymerase chain reaction. Serum levels of RP1L1 protein were evaluated using an ELISA kit. The results were assessed using the statistical analysis method of "IBM SPSS Statistics 23.0". RESULTS: We have found that the RP1L1 rs3924612 C/G genotype increases the odds of the early AMD development in females (p <.05/2). Also, we found that RP1L1 rs3924612 C/G and G/G genotypes increase the odds of the early AMD in the age group of 56-68 years (p < .05/2). Serum RP1L1 levels were evaluated in study groups but no statistically significant associations were found. CONCLUSION: Based on these results we concluded that RP1L1 rs3924612 polymorphism was associated with the early AMD development, but not with the RP1L1 level changes.

SIRT1 Contributes as an Invasiveness Marker in Pituitary Adenoma.

The aim of the study was to find the association between SIRT1 concentration, SIRT1 rs3758391, rs3818292, rs7895833 polymorphisms and clinical manifestations of pituitary adenoma (PA). The study included 108 patients with PA and 216 healthy individuals. Using commercial kits, DNA was extracted from peripheral blood leukocytes. To determine the PA and control group subjects genotypes was used real-time PCR method, for SIRT concentration measurement we used ELISA method. The statistical data analysis was completed using the "BM SPSS Statistics 20.0" software. Results: We performed statistical analysis of SNPs in the patient and healthy controls and patients' subgroups and found statistically significant differences in rs7895833 genotype (A/A, A/G, G/G) distributions between the active PA and control groups (67.9%, 24.6%, 5.7% vs. 72.2%, 27.3%, 0.5%; p = 0.02) Also, the results showed that the rs7895833 G/G genotype is associated with about 13-fold increased odds of active PA development compared to the A/A (OR = 13.95% CI: 1.314-128.632; p = 0.028) and both A/A and A/G genotypes (OR = 12.9; 95% CI: 1.314-126.624; p = 0.028). There is ample evidence that SIRT1 in the pituitary and other target organs modifies the synthesis, secretion, and activity of hormones to trigger adaptive responses, thus we decided to include this in our study. When determining the serum concentration of SIRT1, we did not find a statistically significant difference between the PA group and the control group. SIRT1 serum level was statistically significantly higher in women with PA than in healthy control women (1.115 (3.748) vs. 136 (0.211); p = 0.008). To conclude-SIRT1 rs7895833 G/G genotype is associated with about 13-fold increased odds of active PA development compared to the A/A and both A/A and A/G genotypes. SIRT1 serum levels are higher in women with PA than in healthy women.

ABCA1 rs1883025 and CYP4F2 rs2108622 Gene Polymorphism Association with Age-Related Macular Degeneration and Anti-VEGF Treatment.

Background and Objectives: The age-related macular degeneration (AMD) pathophysiology is multifactorial, as it consists of interactions between aging, genetic, and environmental factors. We aimed to determine a relationship between AMD and the genes controlling lipid metabolism, and to assess its association with treatment results. The purpose was to find the ABCA1 rs1883025 and CYP4F2 rs2108622 gene polymorphisms in patients with exudative AMD (eAMD) treated with anti-VEGF. Materials and Methods: The study enroled 104 patients with eAMD and 201 healthy persons in a control group. The genotyping of rs1883025 and rs2108622 was performed using the RT-PCR method. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before anti-VEGF therapy, then at three and six months during the therapy, using optical coherence tomography (OCT). The patients were grouped to responders and non-responders according to the changes in BCVA and CRT. Results: The T allele at rs1883025 was more frequent in non-responder eAMD patients compared to responder eAMD patients (41.7% vs. 21.1%; p = 0.009). The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the eAMD group and the control group (56.35%, 39.78%, and 3.87% in the eAMD group and 53.33%, 39.05% and 7.62% in the control group, respectively, p = 0.286). The comparison of CRT and BCVA between the rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes (p = 0.030). Conclusion: The rs1883025 T allele was found to play a more significant role in non-responder eAMD patients compared to responder eAMD patients. The rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes.

Association of RAGE rs1800624 and rs1800625 gene polymorphisms with predisposition to optic neuritis and optic neuritis together with multiple sclerosis.

Optic neuritis (ON) is demyelinating acute inflammatory disease which affects the optic nerve. ON is classified as a typical (demyelinating) or an atypical (idiopathic). Patients often complain having a periocular pain or a visual loss. The main factor causing the optic neuritis is still unknown. It is believed that it might be a combination of genetic and environmental factors. As the optic neuritis is an inflammation disease, the RAGE gene was selected as it is a part of the inflammation process. AIM: to determine the relation between RAGE rs1800624 and rs1800625 genotypes of patients who have a manifestation of optic neuritis and optic neuritis with multiple sclerosis together in Lithuanian population and visual acuity recovery. OBJECTIVES: patients with optic neuritis and healthy controls individuals were examined. Genotyping was carried out by using the instrument of real-time polymerase chain reaction called StepOnePlus (AppliedBiosystems). Statistical analysis was performed using IBM SPSS Statistics 20.0 software and free PLINK software (version 1.07). RESULTS: Results indicate that rs1800624 polymorphism is not statistically significant in optic neuritis manifestation (p = .392), while rs1800625 GG genotype is associated with 7.5-fold increased odds of ON development under the codominant model (OR = 7.5; 95% CI:1.796-31.313; p = .006) and with 6.9-fold increased odds under the recessive model OR = 6.862; 95% CI:1.665-28.288; p = .008); and each allele G is associated with 1.9-fold increased odds of ON development under the additive model (OR = 1.879; 95% CI:1.149-3.072; p = .012). The haplotype containing A-G alleles in rs1800624 and rs1800625 was statistically significantly associated with increased risk for ON development (χ2 = 13.23; p < .001). Both polymorphisms do not have statistically significant importance in relation to visual acuity recovery. CONCLUSIONS: RAGE rs1800625 AA genotype decreases the risk of optic neuritis. The single nucleotide polymorphisms RAGE rs1800624 and rs1800625 do not have a statistically significant importance in relation with visual acuity recovery.

IL-9 and IL-10 Single-Nucleotide Variants and Serum Levels in Age-Related Macular Degeneration in the Caucasian Population.

Considering the immunological impairment in age-related macular degeneration (AMD), we aimed to determine the associations of IL-9 rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884 and IL-10 rs1800871, rs1800872, and rs1800896 polymorphisms and their haplotypes, as well as the serum levels of IL-9 and IL-10 with AMD. 1209 participants were enrolled in our study. SNPs were genotyped using TaqMan SNP genotyping assays by real-time PCR method. IL-9 and IL-10 serum levels were evaluated using ELISA kits. Our study results have shown that haplotypes A-G-C-G-G and G-A-T-A-T of IL-9 SNPs are associated with the decreased odds of early AMD occurrence (p = 0.035 and p = 0.015, respectively). A set of rare haplotypes was associated with the decreased odds of exudative AMD occurrence (p = 0.033). Also, IL-10 serum levels were lower in exudative AMD than in controls (p = 0.049), patients with early AMD (p = 0.017), and atrophic AMD (p = 0.008). Furthermore, exudative AMD patients with IL-10 rs1800896 CT and TT genotypes had lower IL-10 serum concentrations than those with wild-type (CC) genotype (p = 0.048). In conclusion, our study suggests that IL-10 serum levels can be associated with a minor allele at IL-10 rs1800896 and exudative AMD. The haplotypes of IL-9 SNPs were also associated with the decreased odds of early and exudative AMD.