Dalia Zaliuniene

The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration

Abstract Background: Matrix metalloproteinases (MMP) are responsible for the degradation of extracellular matrix components and play an important role in the physiological and pathological remodeling of tissues. Purpose: To assess the impact of MMP-2 Rs2285053 (C –> T), MMP-3 Rs3025039 (5A –> 6A), and MMP-9 Rs3918242 (C –> T) single nucleotide polymorphism on the development of early age-related macular degeneration (AMD). Methods: The study group comprised 148 patients with AMD, and the control group enrolled 526 randomly selected persons. The genotyping of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using the real-time PCR method. Results: The frequency of the MMP-2 (−735) C/T and MMP-3 (−1171) 5A/6A genotypes did not differ significantly between the patients with AMD and the control group, while the MMP-9 (−1562) C/C genotype was more frequently detected in patients with AMD than the control group (73.7% vs. 64.6%, p = 0.048). Logistic regression analysis showed that the MMP-9 (−1562) C/C genotype increased the likelihood of developing early AMD (OR = 1.51, 95% CI: 1.01–2.21; p = 0.046). After the subdivision into the groups by age, a significant difference only in the frequency of the MMP-9 (−1562) C/C genotype was found comparing the AMD patients and the control group younger than 65 years (79.7% vs. 66.4%, p = 0.039). Conclusions: Only MMP-9 Rs3918242 (C –> T) single nucleotide polymorphism was found to play a significant role in the development of AMD, and the effect was more pronounced at the age of less than 65 years.

Early Age-Related Macular Degeneration in Patients with Myocardial Infarction

Purpose: To investigate the prevalence of early age-related macular degeneration (AMD) in patients with acute myocardial infarction (MI). Methods: Enrolled in the study were 262 acute MI patients (MI group), aged 40–64 years, as well as 1,155 non-MI persons, aged 40–64 years, from a random sample (reference group) of the Kaunas population. Results: The prevalence of early AMD in the random sample was 7.3%, while in MI patients, the prevalence was 54.5% (P < 0.001). For all age groups, the prevalence of early AMD was significantly (P < 0.005) higher in MI patients than in reference-group persons. In the reference group, the prevalence of early AMD increased significantly with age, whereas no such trend was observed in the MI group. At the 45- to 54-year-olds, the prevalence was significantly higher in males than in females (9.9% vs. 3.7%; P < 0.05) in the reference group, while overall, the prevalence of early AMD in the males and females of the much larger reference group was 8.6% versus 6.2%, respectively (P > 0.05). It increased more with age for females (3.7% and 10.8% at the age 45–54 and 55–64 years, P < 0.05, respectively) while in males, frequency of AMD did not differ significantly between latter age groups (9.9% vs. 11.6%; P > 0.05). Conclusions: We conclude that the prevalence of early AMD is significantly higher in patients with MI than in a random sample of the population.

Role of MMP-2 (-1306 C/T) Polymorphism in Pituitary Adenoma

Purpose. To determine if the frequency of the genotype of MMP-2 (-1306 C/T) Rs243865 has an influence on the development of pituitary adenoma (PA). Methods. The study enrolled n = 84 patients with PA and a random sample of the population n = 318 (reference group). The genotyping test of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. Results. Analysis of MMP-2 (-1306 C/T) gene polymorphism has not revealed any differences in the genotype (C/C, C/T, and T/T) distribution between the PA patients and the reference group (as follows: 50%, 44%, and 6% versus 59.75%, 33.96%, and 6.29%). MMP-2 (-1306) C/C genotype was rarely observed in noninvasive PA compared to healthy controls: 35.1% versus 59.75%; p = 0.0049, as well C/C genotype being more frequently detected in nonrecurrence PA compared to healthy controls: 46.5% versus 59.75%; p = 0.0468. MMP-2 (-1306) C/T genotype was more frequently present in PA females compared to healthy controls females: 49.1% versus 33.66%; p = 0.041. Conclusion. Patients with noninvasive and nonrecurrence pituitary adenoma were the carriers of the C/C genotype significantly more frequently than their control counterparts and the C/T genotype in females was more frequent.

Role of MMP-2 (-1306 C/T) Polymorphism in Age-Related Macular Degeneration.

Abstract Purpose: To determine if the frequency of the MMP-2 (-1306 C/T) genotype has an influence on the development of early age-related macular degeneration (AMD). Methodology: The study enrolled 387 patients with early AMD and a random sample of 682 healthy persons (control group). The genotyping of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. Results: The analysis of the MMP-2 (-1306 C/T) gene polymorphism did not reveal any differences in the genotype distribution between the patients with AMD and the control subjects. When the study population was divided into age groups, the C/C genotype was more prevalent in the AMD patients aged <65 years than those aged ≥65 years (65.19% versus 53.88%, p = 0.0294), and the C/T genotype was more frequent in the AMD patients aged ≥65 years when compared with the AMD patients aged <65 years (40.78% versus 26.52%, p = 0.0037). Moreover, in the female group younger than 65 years, the frequency of the C/C genotype was greater in the AMD group than the control group (75% versus 58.91%, p = 0.0232). Conclusions: This study showed a significantly greater prevalence of the C/C and C/T genotypes in the patients with AMD younger than 65 years and those aged ≥65 years, respectively. Moreover, the AMD women aged <65 years were the carriers of the C/C genotype significantly more frequently than their control counterparts.

Best vitelliform macular dystrophy: literature review

Best vitelliform macular dystrophy (BVD) is a slowly progressive form of macular dystrophy. In most cases this disease begins in childhood although sometimes it can develop in later age. The diagnosis of BVD is based on family history, clinical and electrophysiological findings. Clinical signs are variable, yet the majority of patients have a typical yellow yolk-like macular lesion in the eye fundus. Lesions are usually bilateral, but in rare cases can be unilateral. Atrophy of the macula may develop after many years. The mutations responsible for Best vitelliform macular dystrophy are found in a gene called VMD2, which encodes a transmembrane protein named bestrophin-1 (hBest1) that is a Ca2+-sensitive chloride channel. Most reported cases causing the disease are in exons 2, 4, 6 and 8 in patients with BVD. In this article we discuss the etiology of Best’s vitelliform macular dystrophy, clinical presentation, diagnostics, genetic and current treatment possibilities.

The association of matrix metalloproteinases polymorphisms and interleukins in advanced age-related macular degeneration

ABSTRACT Purpose: To assess the impact of matrix metalloproteinase (MMP)1-1607 1G/2G (rs1799750), MMP7-181 A/G (rs11568818) single-nucleotide polymorphism and systemic cytokins interleukin-1 beta (IL-1β), IL-6 levels on the development of exudative age-related macular degeneration (eAMD) Methodology: The study group comprised 282 patients with eAMD, and the control group enrolled 379 randomly selected persons. The genotyping of MMP1-1607 (rs1799750) and MMP7-181 (rs11568818) was performed by using the polymerase chain reaction-based restriction fragment length polymorphism method. To determine IL-1β and IL-6 serum levels, the immunoenzymatic method with monoclonal antibodies coated plates was performed. Results: MMP1 rs1799750 1G/2G genotype was more frequently found in the development of eAMD. It was associated with a 4.3-fold increased risk for eAMD under the codominant model and a 4.9-fold increased risk for eAMD under the overdominant model. The effect was more pronounced at the age of less than 65 years. IL-1β concentration was significantly higher for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype in eAMD patients compared with control group subjects. Conclusions: MMP1 rs1799750 1G/2G genotype was found to play a significant role in the development of eAMD at the age of less than 65 years. IL-1β concentration was significantly higher in eAMD patients for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype compared with control group subjects.

The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration

ABSTRACT Background: Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in the developed countries. The main pathological change in AMD is the formation of drusen containing 40% of lipids, dominated by esterified cholesterol (EC) and phosphatidylcholine (PC), and protein. Haplotype ε4 of apolipoprotein E (ApoE) acts as a ligand for the low-density lipoprotein receptor and is involved in the maintenance and repair of neuronal cell membranes. Purpose: This study aimed to evaluate the association of AMD with ApoE gene polymorphism variants (rs7412 and rs429358). Methodology: A total of 2133 subjects were enrolled in our research. The study group comprised patients with early AMD (n = 413) and exudative AMD (n = 307), and the control group enrolled randomly selected persons (n = 1413). The genotyping of ApoE (rs7412 and rs429358) was performed using the real-time polymerase chain reaction (PCR) method. Results: Statistical analysis revealed that ApoE 4/2 genotype was less frequently observed in in older patients with exudative AMD compared to older healthy controls (0.4% vs. 4.0%, p = 0.003). Conclusion: Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls. It leads to hypothesis on the protective effect of ApoE 4/2 to develop AMD in the elderly.

Association of retinal nerve fibre layer thickness with quantitative magnetic resonance imaging data of the optic chiasm in pituitary adenoma patients

To evaluate retinal nerve fibre layer (RNFL) thickness in patients with pituitary adenoma (PA) by optical coherence tomography and to compare it with magnetic resonance imaging (MRI) characteristics of pituitary extension. 154 eyes of 77 patients with PA were evaluated. Ophthalmologic evaluation was performed before surgical treatment. Average and per quadrant thickness of peripapillary RNFL (internal limiting membrane to nerve fiber layer/ganglion cell layer) were calculated. Optical coherence tomography was performed in a disc circle mode (layer distance 3.45 mm; 1024 scans). PA was confirmed by MRI scans. Characteristics of the optic chiasm in relation to the suprasellar adenoma were assessed. Suprasellar extension of PA was diagnosed in 55 patients (71.4%). The optic chiasm thickness differed significantly in the groups with and without suprasellar PA extension (p < .001). A weak positive correlation was found between the height of the optic chiasm right side, middle part, left side and visual acuity (r = 0.349; 0.276; 0.307) (p < .001). RNFL thickness around the optic nerve disc measured preoperatively was reduced significantly in all four quadrants in PA patients compared with the control group (p < .001). RNFL thickness was reduced significantly only in the temporal quadrant in PA patients with suprasellar extension compared with the patients without suprasellar extension (p = .009). The temporal RNFL thickness showed the strongest positive correlation with the distance between optic chiasm and PA (r = 0.401, p < .001), while the superior, nasal and, inferior RNFL quadrants showed a weak (r = 0.079; 0.074; 0.113) or not significant (r = 0.351; 0.380; 0.180) correlation with the distance between the optic chiasm and PA. The chiasmal right side, middle part, left side heights correlated significantly with RNFL thickness in all quadrants (p < .05). Our results indicate that suprasellar extension in PA patients causes visual disturbances.

Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL–17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area

ABSTRACT Background: Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. Materials and methods: The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Results: Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380–0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00–39.06) vs. 3.09 (0.02–19.30) and 0.27 (0.00–34.57) vs. 0.75 (0.00–39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49–39.06) mm2 vs. 5.02 (0.03–37.06) mm2, p = 0.006). Conclusions: SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease—an area of macular lesion.