CFH (rs1061170, rs1410996), KDR (rs2071559, rs1870377) and KDR and CFH Serum Levels in AMD Development and Treatment Efficacy.

BACKGROUND: Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not respond optimally to all patients. OBJECTIVE: This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the CFH (rs1061170, rs1410996) and KDR (rs2071559, rs1870377) genes and the association of CFH and KDR serum levels in patients with AMD. RESULTS: A cohort of 255 patients with early AMD, 252 patients with exudative AMD, and 349 healthy controls underwent genotyping analysis, which revealed significant associations between CFH polymorphisms and the risk of exudative AMD. The CFH rs1061170 CC genotype was associated with an increased risk of early AMD (p = 0.046). For exudative AMD, the CFH rs1061170 TC + CC genotype increased odds (p < 0.001), while the rs1410996 GA + AA genotype decreased odds (p < 0.001). Haplotypes of CFH SNPs were associated with decreased odds of AMD. In terms of response to treatment, none of the SNPs were associated with the response to anti-VEGF treatment. We also found that both early and exudative AMD patients had lower CFH serum levels compared to the control group (p = 0.038 and p = 0.006, respectively). Exudative AMD patients with the CT genotype of CFH rs1061170 had lower CFH serum levels compared to the control group (p = 0.035). Exudative AMD patients with the GG genotype of CFH rs1410996 also had lower CFH serum levels compared to the control group (p = 0.021). CONCLUSIONS: CFH polymorphisms influence susceptibility to AMD but do not correlate with a response to anti-VEGF therapy. Further research is imperative to fully evaluate the developmental significance, treatment efficacy, and predictive role in influencing susceptibility to anti-VEGF therapy for KDR and CFH.

Influence of STAT4 Genetic Variants and Serum Levels on Multiple Sclerosis Occurrence in the Lithuanian Population.

Background: Multiple sclerosis (MS) is an autoimmune disease involving demyelination, inflammation, gliosis, and the loss of neurons. MS is a growing global health problem most likely caused by genetic, immunological, and environmental factors. However, the exact etiology of the disease is still unknown. Since MS is related to a dysregulation of the immune system, it could be linked to signal transducer and activator of transcription 4 (STAT4). To fully comprehend the significance of the STAT4 gene and STAT4 serum levels in MS, further research is required. Methods: A total of 200 MS patients and 200 healthy controls participated in the study. Deoxyribonucleic acid (DNA) was extracted using silica-based membrane technology. Polymerase chain reaction was used in real time for genotyping. Using the ELISA technique, serum levels were measured. Results:STAT4 rs7601754 AA genotype and the A allele were statistically significantly less frequent in MS patients (p = 0.003). Also, rs7601754 was associated with 1.9-fold increased odds of MS occurrence (p = 0.004). The rs7601754 AG genotype was more common in males with MS (p = 0.011) and was associated with 2.5-fold increased odds of MS occurrence in males (p = 0.012). STAT4 serum levels were statistically significantly lower in MS patients compared to the control group (p = 0.007). Conclusions:STAT4 rs7601754 increases the odds of MS occurrence. STAT4 serum levels were statistically significantly lower in MS patients compared to the control group.

Generalised Periodontitis: Examining TAS2R16 Serum Levels and Common Gene Polymorphisms (rs860170, rs978739, rs1357949).

The objective of this study was to evaluate and compare the associations between TAS2R16 serum levels and common gene rs860170, rs978739, and rs1357949 polymorphisms in patients affected by generalized periodontitis. The study enrolled 590 patients: 280 patients with periodontitis and 310 healthy controls as a reference group. Patients underwent periodontal examination and radiographic analysis to confirm the periodontitis diagnosis. Blood samples were collected, and the DNA salting-out method was used for DNA extraction from peripheral venous blood. Genotyping of TAS2R16 (rs860170, rs978739, and rs1357949) was performed using real-time polymerase chain reaction (RT-PCR), and serum level analysis was performed for both periodontitis-affected patients and reference group subjects. The analysis of TAS2R16 rs860170 (TT, CT, and CC) showed a statistically significant difference between generalized periodontitis and the reference group (41.8%, 58.2%, and 0% vs. 38.7%, 56.1%, and 5.2%, p < 0.001). TAS2R16 rs860170 (TT, CT, and CC) showed a statistically significant difference between males in generalized periodontitis and reference groups (38.4%, 61.6%, and 0% vs. 32.9%, 56.6%, and 10.5%, p = 0.002). Female-specific analysis showed that the TAS2R16 rs978739 C allele was more frequent in generalized periodontitis compared to the reference group (37.5% vs. 28.7%, p = 0.016). Subjects aged 70 years and older demonstrated a statistically significant difference in TAS2R16 rs860170 (TT, CT, and CC) between generalized periodontitis and the reference group (42.8%, 57.2%, and 0% vs. 38.6%, 53.8%, and 7.6%, p = 0.003). TAS2R16 serum levels were elevated in generalized periodontitis compared to the reference group (0.112 (0.06) ng/mL vs. 0.075 (0.03) ng/mL, p = 0.002). Females carrying the TAS2R16 rs978739 C allele were more prone to generalized periodontitis development. Associations were found between TAS2R16 rs860170 polymorphisms, elevated TAS2R16 serum levels, and generalized periodontitis development.

Association of KDR (rs2071559, rs1870377), CFH (rs1061170, rs1410996) genes variants and serum levels with pituitary adenoma.

INTRODUCTION: Pituitary adenomas (PA) are slow-growing, benign tumors that usually do not metastasize to other body organs. Although they are referred to as benign, tumor growth can eventually put pressure on nearby structures, spread to surrounding tissues, and cause symptoms. The exact cause of PA is unknown, and the pathogenesis is multifactorial. METHODS: Our study included PA patients and healthy volunteers. Genomic DNA was extracted using the DNA salting-out method. All participants were genotyped for the KDR rs2071559, rs1870377, CFH rs1061170, and rs1410996 polymorphisms. Serum levels of KDR and CFH were examined using the ELISA method. RESULTS: The results of the present study showed that KDR rs2071559 A allele was associated with the occurrence of PA, hormonally active PA, invasive PA, and PA without recurrence development. KDR rs1870377 increased the probability of invasive PA and PA recurrence. CFH rs1061170 C allele was associated with hormonally active PA and the T allele was associated with non-invasive PA development. CONCLUSION: KDR rs2071559, rs1870377, and CFH rs1061170 could be potential biomarkers associated with PA.

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.