Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

Effect of ARMS2 gene polymorphism on intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. The ARMS2 gene has been found to be associated with AMD. Currently, intravitreal ranibizumab (IVR) treatment is one of the widely used treatments for neovascular AMD. The aim of this study was to investigate the association between the genotype of ARMS2 rs10490924 polymorphism and IVR treatment responsiveness in patients with neovascular AMD. The study included 39 patients with advanced neovascular AMD (patient group) and 250 healthy individuals with exome sequencing data (control group). The patient group was divided into three subgroups: GG (N = 10), TG (N = 14), and TT (N = 15). Before IVR treatment, all patients had intraretinal or subretinal fluid or both. They received three monthly IVR-injection treatments. One month after the third injection, the patients were evaluated as either "responders" or "non-responders" based on the presence or absence of intraretinal or subretinal fluid or both. The patient subgroups TG and TT had an 8.56- and 39-fold higher risk of AMD, respectively, than patient subgroup GG had. The allele frequency was 0.537 and 0.10 in the patient and control groups, respectively. Within the patient subgroup TT, there was a significant difference between the "responders" and "non-responders" (P = 0.025). In conclusion, in neovascular AMD patients undergoing IVR treatment, TT genotype tended to be a better predictor of good short-term treatment response, compared to the GG and TG genotypes. Further studies using confirmed genetic biomarkers for individualized optimal treatments are required.

Analysis of ELOVL4 and PRPH2 genes in Turkish Stargardt disease patients.

Stargardt disease (STGD) is an inherited genetic eye condition involving bilateral macular dystrophy leading to progressive central vision loss. It is the most common form of autosomal recessive juvenile macular dystrophy. In this study, ELOVL4 and PRPH2 genes were analyzed in 30 STGD probands for genetic variations using next-generation sequencing. In the patient group, two genetic variants in exon 6 of ELOVL4, and three in exon 3 of PRPH2 were detected. All sequence modifications in both ELOVL4 and PRPH2 were recorded, including those of a non-pathogenic nature. In the control group, four different genetic variations were detected in ELOVL4, and five in PRPH2. STGD patients of different ethnicities may carry distinct ELOVL4 and PRPH2 sequence variants. We believe that the genetic variations identified in this study may be related to STGD etiopathogenesis.

Novel visual system homeobox 1 gene mutations in Turkish patients with keratoconus.

The aim of this study was to screen the visual system homeobox 1 (VSX1) gene in Turkish patients with keratoconus (KC). The patient group consisted of 44 patients who had undergone corneal transplant surgery before the age of 30, for advanced and rapidly progressive KC. The control group comprised 250 healthy individuals. We detected two missense mutations, D144N and D295Y, in exon 2 and exon 5 of the VSX1 gene, respectively, using next-generation sequencing analysis. The pathologic effects of the D144N and D295Y missense mutations on protein function were determined with bioinformatic analysis tools, SIFT, PolyPhen, and MutationTaster. Aspartic acid at the 144th position was more preserved among species than aspartic acid at the 295th position of the VSX1 protein. In the control group, five different genetic variations were detected, two of which (rs8123716 and rs12480307) were synonymous with variations in the patient group. Our results suggested that the D144N and D295Y mutations might have a role in the pathogenesis of KC disease.

Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to evaluate and compare the effects of gliclazide-modified release (gliclazide-MR), metformine (MET) and pioglitazone (PIO) monotherapies on glycemic control and conventional/non-conventional cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A single center, randomized, 52-wk comparator-controlled clinical study was carried out in patients with newly diagnosed uncontrolled T2DM. A total of 57 patients were randomized into gliclazide-MR, metformin and pioglitazone groups. Drugs were administered for 12 months. Anthropometric measurements, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin, HOMA-IR, lipid parameters, the markers of coagulation/fibrinolysis, inflammation and endothelial dysfunction were measured at baseline and at months 3, 6, and 12. RESULTS: In the gliclazide-MR group, HC, FPG, HbA1c, insulin, HOMA-IR, TC, trigylcerides, Lp (a), E-selectin and Hcy were significantly decreased after treatment compared to baseline. In the MET group, BMI, WC, FPG, PPG, HbA1c, ICAM-1 and Hcy significantly decreased after treatment compared to baseline. In PIO group, WC, HC, FPG, PPG, HbA1c, C-peptid, HOMA-IR, trigylcerides, vWF, IL-6, ICAM-1, E-selectin and Hcy significantly decreased after treatment compared to baseline, whereas, HDL-C increased. At the end of the month 12, the decreases in insulin and HOMA-IR score were more pronounced with PIO compared to gliclazide. CONCLUSIONS: Gliclazide-MR, MET and PIO monotherapies, were equally effective in proving glycemic control in patients with newly diagnosed, oral antidiabetic (OAD)-naive T2DM. But, improvements in conventional/non-conventional cardiovascular risk factors were more pronounced in patients on PIO therapy compared to gliclazide and MET therapies. Also, all of the 3 drugs represent effective and safe first-line pharmacological treatment options in these patients.

Reactions of connective tissue to compomers, composite and amalgam root-end filling materials.

AIM: To evaluate the subcutaneous connective tissue reaction to compomers, composite and amalgam root-end filling materials. METHODOLOGY: This study was conducted in 30 Wistar albino rats. The materials were mixed or light-cured according to the manufacturer's directions and placed in polyethylene tubes. Group 1 - Dyract compomer (Dentsply); group 2 - F2000 compomer (3M); group 3 - Valux Plus composite (3M); group 4 - Oralloy high-copper amalgam (Coltene). The tubes containing the materials were implanted into the dorsal connective tissue of rats, which were killed 7, 15, 30, 60 and 90 days after the implantation procedure. Thirty extra empty tubes were also placed as controls. The implant sites were excised and prepared for histological evaluation. Sections of 6-microm thickness were stained with haematoxylin and eosin and assessed under light microscopy. The presence of inflammation, predominant cell type and thickness of fibrous connective tissue adjacent to each implant were recorded. Reactions were scored as: 0: none or few cells and no reaction; 1: less than 25 cells and mild reaction; 2: between 25 and 125 cells and moderate reaction; 3: 125 and more cells and severe reaction. Fibrous capsules were considered to be thin if their thickness was less than 150 microm and thick if it was more than 150 microm. Necrosis and formation of calcification were categorized as 'yes' or 'no'. RESULTS: All four materials caused moderate or severe inflammatory reactions in the first 7-day period, but these reactions decreased by the 60th and 90th days. No significant difference in inflammatory cell numbers between the materials could be detected at the 90th day. CONCLUSIONS: Valux Plus composite, Dyract and F2000 compomers and Oralloy amalgam were biocompatible.