Relative Leukocyte Telomere Length and Telomerase Complex Regulatory Markers Association with Leber's Hereditary Optic Neuropathy.

Background and Objectives: To evaluate the association of relative leukocyte telomere length (RLTL) and telomerase complex regulatory markers with Leber's hereditary optic neuropathy (LHON). Material and Methods: A case-control study was performed in patients with LHON (≥18 years) and healthy subjects. The diagnosis of LHON was based on a genetic blood test (next-generation sequencing with Illumina MiSeq, computer analysis: BWA2.1 Illumina BaseSpace, Alamut, and mtDNA Variant analyzer 1000 were performed) and diagnostic criteria approved by the LHON disease protocol. Statistical analysis was performed using the standard statistical software package, IBM SPSS Statistics 27. Statistically significant results were considered when p < 0.05. Results: Significantly longer RLTL was observed in LHON patients than in healthy controls (p < 0.001). RLTL was significantly longer in women and men with LOHN than in healthy women and men in the control group (p < 0.001 and p = 0.003, respectively). In the elderly group (>32 years), RLTL was statistically significantly longer in LHON patients compared with healthy subjects (p < 0.001). The GG genotype of the TERC rs12696304 polymorphism was found to be statistically significantly higher in the LHON group (p = 0.041), and the C allele in the TERC rs12696304 polymorphism was found to be statistically significantly less common in the LHON group (p < 0.001). The RLTL of LHON patients was found to be statistically significantly longer in the TERC rs12696304 polymorphism in all tested genotypes (CC, p = 0.005; CG, p = 0.008; GG, p = 0.025), TEP1 rs1760904 polymorphism in the GA genotype (p < 0.001), and TEP1 gene rs1713418 in the AA and AG genotypes (p = 0.011 and p < 0.001, respectively). Conclusions: The RLTL in LHON patients was found to be longer than in healthy subjects regardless of treatment with idebenone. The TERC rs12696304 polymorphism, of all studied polymorphisms, was the most significantly associated with changes in LHON and telomere length.

A Typical Case Presentation with Spontaneous Visual Recovery in Patient Diagnosed with Leber Hereditary Optic Neuropathy due to Rare Point Mutation in MT-ND4 Gene (m.11253T>C) and Literature Review.

Leber hereditary optic neuropathy (LHON) is one of the most common inherited mitochondrial optic neuropathies, caused by mitochondrial DNA (mtDNA) mutations. Three most common mutations, namely m.11778G>A, m.14484T>G and m.3460G>A, account for the majority of LHON cases. These mutations lead to mitochondrial respiratory chain complex I damage. Typically, LHON presents at the 15-35 years of age with male predominance. LHON is associated with severe, subacute, painless bilateral vision loss and account for one of the most common causes of legal blindness in young individuals. Spontaneous visual acuity recovery is rare and has been reported in patients harbouring m.14484T>C mutation. Up to date LHON treatment is limited. Idebenone has been approved by European Medicines Agency (EMA) to treat LHON. However better understanding of disease mechanisms and ongoing treatment trials are promising and brings hope for patients. In this article we report on a patient diagnosed with LHON harbouring rare m.11253T>C mutation in MT-ND4 gene, who experienced spontaneous visual recovery. In addition, we summarise clinical presentation, diagnostic features, and treatment.

SIRT1 (rs3740051) role in pituitary adenoma development.

BACKGROUND: Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA). METHODS: The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method. RESULTS: Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099-0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091-0.575; p = 0.002) were associated with lower odds of occurring an invasive PA. CONCLUSIONS: Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.

Changes of visual functions in patients with pituitary adenoma.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate associations between visual functions (visual acuity, perimetry, optic nerve disc condition, and color contrast sensitivity) and pituitary adenoma (PA) diameter. MATERIAL AND METHODS: In the study, 20 patients with PA, which was confirmed by computed tomography or magnetic resonance imaging scans, were examined. The patients were divided into 2 groups: those with a PA diameter of ≤1 cm (14 eyes) and with a PA diameter of >1 cm (26 eyes). The control group comprised 40 healthy age- and gender-matched persons (80 eyes). The diameter of PA, visual acuity, and perimetry were analyzed; the F-M 100 hue test for color discrimination was used in patients with PA. RESULTS: Visual acuity was better in the control group as compared with both groups of patients (1.0 vs. 0.90 [SD, 0.50] and 0.64 [SD, 0.21]; P=0.01; respectively). The results of the Farnsworth-Munsell 100 hue test were also better in the control group compared with the patients with PA of ≤1 cm and >1 cm (error score of 80.1 [SD, 53.0] vs. 131.8 [SD, 30.6] and 244.68 [SD, 51. 6], respectively; P=0.011). There was a very strong positive correlation between the error score of the F-M 100 hue test and PA diameter (r=0.905), but the correlation between the error score and visual acuity (r=-0.32), perimetry (r=0.21), and eye fundus changes (r=0.36) and PA diameter was weak. CONCLUSIONS: Our results showed that PA can cause the impairments of visual acuity, perimetry, and color contrast sensitivity. The computerized F-M 100 hue test can be one of the methods for an early diagnosis of chiasm damage in patients with PA.

Clinical Overview of Leber Hereditary Optic Neuropathy.

Leber hereditary ptic neuropathy (LHON) is a disease of young adults with bilateral, painless, subacute visual loss. The peak age of onset of LHON is in the second and third decades of life. Men are 4 times more likely to be affected than women. In about 25-50% of cases, both eyes are affected simultaneously. In unilateral cases, the other eye is usually affected 2 to 3 months later. Visual acuity deteriorates to counting fingers or worse with a dense central or centrocecal scotoma. In the subacute phase, the optic disc may appear hyperemic with swelling of the peripapillary retinal nerve fibre layer, peripapillary telangiectasias, and increased vascular tortuosity. Ocular coherence tomography of the macula shows marked thinning of the ganglion cell complex even at this stage. The diagnosis of LHON is made in a subject with a consistent clinical history and/or one of three common pathogenic mitochondrial DNA (mtDNA) variants identified by molecular genetic testing. Idebenone was approved by the European Medicines Agency under exceptional circumstances for the treatment of LHON. Current evidence suggests some benefit to vision in a subset of affected individuals treated with idebenone, particularly when treated within the first year of onset of vision loss. In this article, we discuss aetiology, clinical features, diagnosis, differential dignosis, prognosis and treatment.

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.

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).

IL-10 Gene Rs1800871, Rs1800872, and Rs1800896 Polymorphisms and IL-10 Serum Levels Association with Pituitary Adenoma.

The aim and objective of this study is to determine the association between the rs1800871, rs1800872, and rs1800896 polymorphisms of the gene IL-10 and the serum levels of IL-10 in patients with pituitary adenoma. METHODS: Data from 106 patients with pituitary adenoma and 192 control patients were used for the study. DNA was isolated from peripheral blood using the salt precipitation method. The samples were genotyped in real-time using the polymerase chain reaction method. IL-10 serum levels were evaluated using an ELISA kit. The data obtained were systematized using the computer program IBM SPSS Statistics. RESULTS: The AG genotype of IL-10 rs1800871 was statistically significantly lower in the inactive PA group than in the control group (22.7% vs. 40.6%, p = 0.027). The TG genotype of IL-10 rs1800872 was also statistically significantly lower in the inactive PA group than in the control group (22.7% vs. 40.6%, p = 0.027). A binary logistic regression analysis of the polymorphisms in the IL-10 gene in PA and control groups based on the pituitary adenoma activity showed that the AG genotype of IL-10 rs1800871 increased the chance of inactive PA by 2.2-fold in codominant (OR: 2.272, CI: 1.048-4.925, p = 0.038) and overdominant (OR: 2.326, CI: 1.086-4.982, p = 0.030) models. Moreover, the TG genotype of IL-10 rs1800872 increased the probability of inactive PA by 2.2-fold in codominant (OR: 2.272, CI: 1.048-4.925, p = 0.038) and overdominant (OR: 2.326, CI: 1.086-4.982, p = 0.030) models. The association of the IL-10 polymorphisms with PA invasiveness and recurrence in PA and control groups did not yield statistically significant results. CONCLUSIONS: IL-10 rs1800871 and IL-10 rs1800872 may be associated with the development of inactive PA.

TBX15 rs98422, DNM3 rs1011731, RAD51B rs8017304, and rs2588809 Gene Polymorphisms and Associations With Pituitary Adenoma.

BACKGROUND: Pituitary adenoma (PA) is a benign tumor of parenchymal cells in the adenohypophysis, and it's development is strongly associated with genetic factors.This study aim was to find whether TBX15 rs98422, DNM3 rs1011731, RAD51B rs8017304, and rs2588809 single nucleotide polymorphisms can be associated with pituitary adenoma. While the TBX15 gene belongs to the T-box family of genes and is a transcription factor involved in many developmental processes, the DNM3 encodes a protein that is a member of the dynamin family with mechanochemical properties involved in actin-membrane processes, predominantly in membrane budding, and the RAD51B gene plays a significant role in homologous recombination in DNA repair for genome stability. MATERIALS AND METHODS: The study enrolled 113 patients with pituitary adenoma and 283 healthy control subjects. DNA samples were extracted and purified from peripheral blood leukocytes. Genotyping was carried out using real-time polymerase chain reaction. The results were assessed using binomial logistic regression. RESULTS: Our study revealed that RAD51B rs2588809 TT genotype could be associated with PA development in the co-dominant (OR=6.833; 95% CI=2.557-18.262; p<0.001) and recessive (OR=7.066; 95% CI=2.667-18.722; p<0.001) models. The same results were observed in females but not in males and PA without recurrence, while in PA with recurrence, no statistically significant results were obtained. CONCLUSION: RAD51B rs2588809 TT genotype may increase the odds of PA development in women; it may also be associated with non-recurrent PA development.

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.

Do TRIB1 and IL-9 Gene Polymorphisms Impact the Development and Manifestation of Pituitary Adenoma?

BACKGROUND/AIM: To evaluate the association between TRIB1(rs6987702) and IL-9(rs1859430, rs2069870) genotypes with the development and manifestation of pituitary adenoma (PA). MATERIALS AND METHODS: The study group included 141 patients with PA and the control group consisted of 287 healthy people. The genotyping of rs6987702, rs1859430 and rs2069870 was carried out using a real-time polymerase chain reaction. RESULTS: Statistically significant results were obtained regarding the rs1859430, but there were no significant results regarding rs6987702. We found that the rs1859430 A/A genotype increased the odds of having recurrent PA six times (p=0.006) under the co-dominant model and four times (p=0.021) under the recessive model. Furthermore, the analysis showed that the G/A genotype increased the odds of having recurrent PA 2.3 times (p=0.003) under the co-dominant model, while G/A and A/A genotypes increased the odds 2.7 times (p=0.011) under the over-dominant model. CONCLUSION: Certain genotypes of rs1859430 can be associated with PA recurrence.

Associations of cholesteryl ester transfer protein (CETP) gene variants with pituitary adenoma.

AIM: The aim was to evaluate the association of CETP (rs5882 and rs708272) single nucleotide polymorphisms with the presence, invasiveness, hormonal activity and recurrence of pituitary adenoma (PA). METHODS: The study group included 142 patients with PA and the control group, 753 healthy subjects. The genotyping of CETP (rs5882 and rs708272) was performed using a real-time PCR method. RESULTS: After statistical analysis we found that CETP rs708272 genotype G/A under the over-dominant model was associated with the decreased odds of PA (OR=0.637; 95%CI: 0.443-0.917; P=0.015), active PA (OR=0.538; 95%CI: 0.335-0.865; P =0.01) and non-recurrent PA (OR=0.602; 95% CI: 0.402 - 0.902; P =0.014). When compared to controls, the rs708272 genotype G/A was less frequent in the active PA subgroup (37.5% vs 52.7%, P =0.009) and the non-recurrent PA subgroup (40.2% vs 52.7%, P=0.013), while the rs5882 genotype A/A was less frequent in the non-recurrent PA subgroup (37.5% vs 46.2%, P=0.015). CONCLUSION: Our study showed that CETP rs708272 genotype G/A may be associated with a decreased risk of PA.

Association of ApoE haplotype with clinical evidence of pituitary adenoma.

PURPOSE: To evaluate the association of the presence, invasiveness, hormonal activity and recurrence of pituitary adenoma (PA) with ApoE genotypes and alleles. MATERIALS AND METHODS: Our study group included 142 patients with PA and the control group included 256 healthy individuals. The genotyping of ApoE (rs7412 and rs429358) was performed using a real-time PCR method. RESULTS: After statistical analysis we found that ApoE genotype E2/E3 was associated with 2.6-fold increased odds of active PA (OR = 2.609; 95%CI: 1.380-4.932; p = 0.003), while the presence of ApoE E3/E3 decreased odds of active PA by 65% (OR = 0.343; 95%CI: 0.205-0.575; p < 0.001). The frequency of the allele ε3 was lesser in the PA group (74.3% vs. 83%, p = 0.003) when compared to controls but it was statistically significantly more frequent in the invasive PA than in the noninvasive PA subgroup (80.4% vs. 65.5%, p = 0.005). The ApoE E2/E4 genotype was more frequent in the noninvasive PA subgroup (10.3% vs. 0%, p = 0.003) than in the invasive PA subgroup. The ApoE E4/E4 genotype was more frequent in the recurrent than in the non-recurrent PA subgroup (6.6% vs. 0%, p = 0.006). No associations between ApoE polymorphisms and Ki-67 labelling index were found. CONCLUSION: The ApoE E2/E3 genotype is associated with the presence of PA while the ApoE genotype E2/E4 is associated with noninvasive PA development. The allele ε3 could possibly have a protective effect against PA. The genotype E4/E4 is associated with the development of recurrent PA.

[Comparison of postoperative results after implantation of hydrophilic acrylic or hydrophobic acrylic intraocular lens: data of one-year prospective clinical study]. / Akriliniu hidrofiliniu ir akriliniu hidrofobiniu intraokuliniu lesiu pooperaciniu rezultatu palyginimas (prospektyviojo klinikinio tyrimo vieneriu metu duomenys).

OBJECTIVE: To evaluate and compare the impact of two sharp-edge optic foldable intraocular lenses (IOLs) of similar design made from different material (hydrophilic acrylic or hydrophobic acrylic) on visual function, anterior and posterior capsule opacification at one-year follow-up after cataract phacoemulsification. MATERIAL AND METHODS: Seventy-two eyes of 72 patients scheduled for cataract surgery were included in a prospective clinical study. Two foldable sharp-edge optic posterior chamber acrylic IOLs of similar design were used. Thirty-nine eyes of 39 patients received a single-piece hydrophilic acrylic (PC 511, Ophtec) IOL and 33 eyes of 33 patients - single-piece hydrophobic acrylic (AcrySof, SA60AT, Alcon) IOL. Visual acuity, anterior capsule opacification (ACO), capsulorrhexis/optic overlapping, and posterior capsule opacification (PCO) were evaluated. The intensity of ACO was assessed subjectively. PCO values in the entire IOL optic area and in the central 3-mm optic zone were assessed using a photographic image analysis system (EPCO 2000). The patients were examined at one year postoperatively. RESULTS: There were no significant differences in best-corrected visual acuity and capsulorrhexis/optic overlapping between IOL types at 1-year follow-up after surgery. In the single-piece hydrophilic acrylic IOL group, the grade of ACO density was significantly higher in capsulorrhexis rim area (1.56+/-0.71 and 1.00+/-0.75) and in the capsule/optic area (1.62+/-0.67 and 1.00+/-0.75) (P<0.05). PCO values of the entire IOL optic area (0.12+/-0.13 and 0.024+/-0.02) as well as in the central 3-mm optic zone (0.06+/-0.11 and 0.001+/-0.003) was significantly higher in the single-piece hydrophilic acrylic IOL group one year postoperatively (P<0.05). In 33.3% of cases of the single-piece hydrophilic acrylic IOL group, contraction of haptics to IOL optics was present one year postoperatively, which was not present in any case of the single-piece hydrophobic acrylic IOL group. CONCLUSIONS: One-year follow-up after cataract surgery has shown a significant difference in ACO and PCO development comparing single-piece hydrophilic acrylic and single-piece hydrophobic acrylic intraocular lenses. The effect of hydrophobic acrylic foldable lenses on preventing anterior and posterior capsule opacification is mainly a result of the acrylic hydrophobic biomaterial.

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 Optic Neuritis with CYP4F2 Gene Single Nucleotide Polymorphism and IL-17A Concentration.

BACKGROUND: The aetiology and pathophysiology of optic neuritis (ON) is not absolutely clear but genetic and inflammatory factors may be also involved in its development. The aim of the present study was to determine the influence of single nucleotide polymorphism (SNP) of CYP4F2 (rs1558139) and serum levels of IL-17A on ON development. MATERIALS AND METHODS: Forty patients with ON and 164 control subjects were evaluated. Patients were divided by gender, also ON patients were divided into two subgroups: ON with and without multiple sclerosis (MS). CYP4F2 rs1558139 was genotyped using real-time PCR. Serum IL-17A levels were measured using ELISA IL-17A kits. RESULTS: We found that A/A genotype of CYP4F2 rs1558139 was statistically significantly more frequent in men with ON and MS than in women: 57.1% versus 0%, p = 0.009. Also, allele A was statistically significantly more frequent in men with ON and MS than in women: 71.4% versus 37.5%, p = 0.044. Serum levels of IL-17A were higher in ON group than in control group: (median, IQR): 20.55 pg/ml, 30.66 pg/ml versus 8.97 pg/ml, 6.24 pg/ml, p < 0.001. CONCLUSION: The higher IL-17A levels were found to be associated with ON, while allele A at rs1558139 was associated only with ON with MS in male patients.

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.

N-myc downstream-regulated gene 2 (NDRG2) promoter methylation and expression in pituitary adenoma.

BACKGROUND: Pituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Several studies have shown N-myc downstream regulated gene 2 (NDRG2) as a tumor suppressor gene, but the role of NDRG2 gene in pituitary adenoma pathogenesis has not been elucidated. The aim of our research has been to examine NDRG2 mRNA expression in PA and to determine the associations between the NDRG2 gene epigenetic changes and the development of recurrence or invasiveness of PA and patient clinical data. METHODS: The MS-PCR was used for NDRG2 promoter methylation analysis and gene mRNA expression levels were evaluated by qRT-PCR in 68 non-functioning and 73 functioning adenomas. Invasiveness was evaluated using magnetic resonance imaging with Hardy's modified criteria. Statistical analysis was performed to find correlations between NDRG2 gene mRNA expression, promoter methylation and patient clinical characteristics and PA activity. RESULTS: The NDRG2 mRNA expression was significantly lower in the case of acromegaly (GH and IGF-1 hypersecretion) than in other diagnoses of PAs (p < 0.05). Also, the NDRG2 expression was significantly higher in prolactinoma (PRL hypersecretion) than in in other diagnoses of PAs (p < 0.05). The promoter of NDRG2 was methylated in 22.69% (12/58 functioning and 15/61 non-functioning) of patients with PA. However, the NDRG2 gene mRNA expression was not significantly related to its methylation status. Clinical factors, such as: age, gender, relapse and diagnoses of Cushing syndrome were of no significance for NDRG2 promoter methylation and mRNA expression levels, as well as secreting or non-secreting PAs and the invasiveness of PAs. CONCLUSION: The different NDRG2 promoter methylation and expression levels in PA samples showed tumor heterogeneity and indicates a potential role of this gene in pituitary adenoma pathogenesis, but the corresponding details require intensive research.

Association of FGFR2 rs2981582, SIRT1 rs12778366, STAT3 rs744166 gene polymorphisms with pituitary adenoma.

The aim of the present study was to determine the association between sirtuin 1 (SIRT1), fibroblast growth factor receptor 2 (FGFR2) and signal transducer and activator of transcription 3 (STAT3) polymorphisms, and pituitary adenoma (PA) development, invasiveness, hormonal activity and recurrence. The present study included 143 patients with a diagnosis of PA. The reference group involved 808 healthy subjects. The genotyping of SIRT1 rs12778366, FGFR2 rs2981582 and STAT3 rs744166 was performed using the quantitative polymerase chain reaction method. The SIRT1 rs12778366 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and control group subjects. The rs12778366 T/C genotype was observed to be different in non-invasive, non-recurrent and inactive PA subgroups compared with the control group, while the C/C genotype was observed to be different in invasive, recurrent and active PA subgroups compared with the control group. STAT3 rs744166 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and the control groups. The rs744166 G/G genotype was observed to be different in invasive, non-recurrent and active PA subgroups compared with the control group, while the rs744166 A/A genotype was observed to be different in the active PA subgroup compared with the control group, and was also different in terms of invasiveness and recurrence in PA subgroups. The present study demonstrated that SIRT1 rs12778366 is associated with pituitary adenoma development while STAT3 rs744166 is associated with PA invasiveness, hormonal activity and recurrence.

The role of MMP-1 and FGFR4-R388 gene polymorphisms in pituitary adenoma.

BACKGROUND: The pathogenesis of pituitary adenoma (PA) is complex and poorly understood. It is thought that PA has a multifactorial aetiology; genetic factors also have an impact on PA development. Since MMP1 and FGFR4 genes play an important role in tumour growth, differentiation and progression, we decided to determine if the frequency of the genotypes of MMP-1 and FGFR4-R388 polymorphisms influence the development of PA. MATERIALS AND METHODS: The study enrolled n = 100 patients with PA and n = 200 healthy controls (reference group). The genotyping tests of MMP-1 and FGFR4-R388 were carried out using the real-time polymerase chain reaction (PCR) method. RESULTS: The polymorphism in the MMP-1 gene 1G/1G genotype was more frequent in the group of invasive PA than in the control group: 28.6% vs. 16.5%, p = 0.044. The 1G/2G genotype was more frequent in females of the control group compared to PA group females: 50.3% vs. 30.8%, p = 0.011. The polymorphism in the MMP-1 gene 1G/1G genotype was more frequent in the active PA group than in the control group: 28.4% vs. 16.5%, p = 0.044. FGFR4-R388 did not play any predominant role in PA development. CONCLUSION: The MMP-1 gene 1G/1G may play a role in invasive and active PA development.