NEW GENETIC MARKERS ASSOCIATED WITH SUSCEPTIBILITY TO EXFOLIATION SYNDROME AMONG GEORGIAN POPULATION.

The aim of this study was to identify susceptibility variants of CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A genes for Exfoliation Syndrome (XFS) and Exfoliation Glaucoma (XFG) by a case-control association study approach among Georgian population. Self-reported Georgian subjects were recruited between 2015 and 2017 at a specialized ophthalmic center. Patients underwent detailed ophthalmic examination to diagnose or exclude Exfoliation Syndrome and Exfoliation Glaucoma. Patients underwent peripheral blood sampling. Genome-Wide Association Study (GWAS) was performed using Illumina OmniExpress Microarray (USA). One hundred and thirty-two XFS patients (including XFG-affected individuals) and 199 healthy subjects were included into the study. Six genes CACNA1A rs4926244, POMP rs7329408, TMEM136 rs11827818, AGPAT1 rs3130283, RBMS3 rs12490863 and SEMA6A rs10072088 variants were identified. The A alleles of SEMA6A and POMP genes are likely the risk factors of disease development in Georgians with p=0.001; OR= 1.8, 95% CI 1.2676 to 2.6973 and p=0.001; OR=1.6, 95% CI 0.9931 to 2.5634, respectively. SEMA6A homozygotes have 4 times greater risk compared to normal individuals, with p<0.004; OR=4.0, 95% CI 1.1531 to 13.9903. The G allele of CACNA1A in homozygous state increases the risk up to 3-fold with p<0.05, OR=3.15, 95% CI 0.9275 to 10.6658. The A alleles of SEMA6A and POMP increased XFG susceptibility more than 3 times (p=0.04; OR= 3.4; 95% CI: 1.2676 to 2.6973 and p=0.02; OR= 2.7; 95% CI: 0.9931 to 2.5634, respectively). Three high-risk genes have been identified in connection to XFS in Georgian population. Two genes are relevant to XFG. Three other previously described genes are not associated with the disease development.

LOXL1 GENE VARIANTS IN ASSOCIATION WITH EXFOLIATION SYNDROME IN GEORGIAN POPULATION.

The aim of this study was to identify susceptibility variants of LOXL1 gene for Exfoliation Syndrome and Exfoliation Glaucoma by a case-control association study approach in Georgian population. Self-reported Georgian subjects were recruited between 2015 and 2017 at a specialized ophthalmic center. Patients underwent detailed ophthalmic examination to diagnose or exclude Exfoliation Syndrome (XFS) and Exfoliation Glaucoma (XFG). Patients underwent peripheral blood sampling. Genome-Wide Association Study (GWAS) was performed using Illumina OmniExpress Microarray. One hundred and thirty-two XFS patients and 195 healthy subjects were included into the study. Four LOXL1 variants were identified: rs2165241, rs3825942 (G153A), rs4886776 (R141L) and rs8042039 (G153D). Allele A of rs2165241 and allele G of rs3825942 are likely the main risk factors of disease development in Georgians with p=0.0001; OR= 5.8; 95% CI: 1.9986-16.9372 and p=0.002; OR=4.6; 95% CI: 1.7531-12.3146, respectively, both present in 96% of affected patients. The above-mentioned alleles are also encountered in more than 80% of healthy individuals. Two other SNPs have been described for the first time in exfoliation patients, though they appear to have no effect on the disease development in Georgian population. Two high-risk alleles of LOXL1 gene have been identified in Georgian population. As these SNPs are also very prevalent in healthy subjects, further studies are needed to identify the genetic mechanisms of exfoliation syndrome and exfoliation glaucoma.

[Shifts in the heart left ventricle function in patients with pulmonary tuberculosis during adequate chemotherapy].

To investigate the hemodynamics and myocardic contraction of the heart left ventricle, 61 patients with pulmonary tuberculosis (main group) and 26 healthy subjects (control group) were observed. Higher ultimate systolic and diasystolic volumes of the left ventricle and lower levels of the efflux fraction in the patients with active pulmonary tuberculosis were stated. There was shown inverse correlation of the systemic systolic arterial pressure and the left ventricle efflux fraction with ESR, evident of the tuberculosis intoxication. The most pronounced aggravation of the left ventricle function was recorded in the patients with the most severe tuberculosis process. The impairments in the left ventricle in the patients with active pulmonary tuberculosis were of functional nature. Due to intensive therapy of the tuberculosis, the indices of the left ventricle efflux function improved and the systemic arterial pressure came to normal, along with elimination of the tuberculosis intoxication signs.

[Hemodynamic features in persons with posttuberculosis pulmonary changes].

The specific intravascular and central hemodynamic features were studied in 42 patients with pronounced posttuberculous changes in the lung in comparison to a group of healthy individuals without a history of tuberculosis. Along with clinical, functional, and electrocardiographic studies, the authors used echocardiography. End ventricular and atrial systolic and diastolic areas, end left ventricular systolic and diastolic volume, ejection fraction, stroke and cardiac indices were determined. Dilation of the right ventricle and right atrium and their increased specific contractility were ascertained in patients with pronounced posttuberculous changes. At the same time hypertrophy of the right ventricular wall was rarely observed. This gives grounds to regard dilatation of the right ventricle as an earlier sign of evolving chronic cor pulmonale that its hypertrophy. There were no changes in the left ventricle, left atrium, ejection fraction, stroke and cardiac indices, which was explained by the absence of intoxication and toxic infective action in the persons clinically recovered from tuberculosis.

[A program of prevention of dysplastic arthrosis (general principles)]. / Programma profilaktiki displasticheskogo artroza (obshchie predposylki).

The authors put forward a program of prevention of dysplastic arthrosis which is presented in graphic form with textual description. It has been worked out on the basis of the formerly elaborated conceptual model "Dysplasia of the joint-dysplastic arthrosis" and it is a complex of general medical prophylactic measures oriented towards the elimination of mutagenous environmental factors, i.e. towards prevention of morbidity and towards the treatment-and-rehabilitation orthopaedic measures directed at reduction of the risk of development of dysplastic arthrosis in the conditions of dysplastic lesion of the joint (prevention of the disease). The conditions necessary for carrying out this program are supposed to be: a diagnostic algorithm providing for revealing dysplastic lesions already at the preclinical stage; thorough quantitative and qualitative characteristics of the dysplastic process providing for planning of correct surgical interventions; prognostic evaluations presuming a probability of evolution of the dysplastic process and its outcome; and a system of stage-by-stage diagnostic and treatment-and-rehabilitation measures providing for achievement of the effect expected in each particular case. Three groups of surgical interventions have been pointed out: prophylactic, which are performed on the dysplastic joint in case of absence of dystrophic changes; therapeutic, which are performed in case of presence of reversible dystrophic changes (e.g. chondromalation at stages I and II); and palliative, which only result in temporary stabilization of the arthrosis process, i.e. leading to improvement.