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1.
Sovrem Tekhnologii Med ; 15(2): 60-70, 2023.
Article in English | MEDLINE | ID: mdl-37389024

ABSTRACT

The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation. Materials and Methods: The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. Results: Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes. Conclusion: Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.


Subject(s)
Pancreatitis, Chronic , Trypsin Inhibitor, Kazal Pancreatic , Humans , Adult , Trypsin Inhibitor, Kazal Pancreatic/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Alleles , Exons , Pancreatitis, Chronic/genetics , Trypsin/genetics , Trypsinogen
2.
Article in Russian | MEDLINE | ID: mdl-32490622

ABSTRACT

OBJECTIVE: To compare apolipoprotein E (APOE) genotypes with outcomes and levels of neuromarkers in children with severe traumatic brain injury (TBI). MATERIAL AND METHODS: APOE polymorphisms were genotyped in 69 children with severe TBI. The following markers of brain damage were identified: neuron-specific enolase (NSE), glial protein S100b, content of autoantibodies (aAB) to glutamate receptors (to the NR2 subunit of NMDA receptors), aAB to S100b and brain-derived neurotrophic factor (BDNF). RESULTS AND CONCLUSION: There was no association between APOE 3/3, 3/4, 3/2 genotypes and outcomes assessed by the Glasgow Outcome Scale (GOS). The greatest number of favorable outcomes was noted in the group of APOE 3/3 genotype carriers (60%). The ratio of favorable outcomes to unfavorable outcomes was equal (50%:50%) in groups with APOE 3/4 and APOE 3/2 genotypes. An association between APOE polymorphism and BDNF was found: there were normal BDNF levels in the APOE 3/3 group and reduced levels in the APOE 3/2 group. The correlation between neuromarkers and GOS scores was shown for BDNF and aAB to S100b. In children with favorable TBI outcomes, normal BDNF levels and a lower level of aAB to S100b were observed. Regardless of APOE genotypes, almost all children with severe TBI (95%) showed a significant increase in aAB to glutamate receptors in the remote period and most children had an increase in aAB to S100b in the blood. This fact can be explained by the presence of cerebral hypoxia, activation of autoimmune processes and increased BBB permeability, which may be enhanced by increased NO content and intensification of oxidative processes in children with severe TBI.


Subject(s)
Brain Injuries, Traumatic , Brain , Child , Humans , Polymorphism, Genetic , Prognosis , S100 Calcium Binding Protein beta Subunit
3.
Urologiia ; (5): 140-143, 2019 Dec.
Article in Russian | MEDLINE | ID: mdl-31808650

ABSTRACT

Primary hyperoxaluria is a group of inherited metabolic diseases characterized by increased formation of calcium-oxalate stones in kidneys with development of nephrolithiasis and chronic kidney disease. The article summarizes the modern information on the diagnostics and treatment of the disorder depending on genotype of the patient (AGXT, GRHPR, HOGA1 genes). The evaluation of the molecular genetic aetiology of the kidney stone disease contributes to the personalized treatment and prevention of the pathology in the patients and their relatives.


Subject(s)
Genetic Predisposition to Disease , Hyperoxaluria, Primary/diagnosis , Hyperoxaluria, Primary/genetics , Kidney Calculi/genetics , Genotype , Humans , Hyperoxaluria, Primary/therapy , Kidney/physiopathology , Molecular Biology , Phenotype
4.
Bull Exp Biol Med ; 167(4): 533-535, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31502125

ABSTRACT

A model of moderate hyperhomocysteinemia associated with mechanical injury of the musculoskeletal system was developed and experimentally substantiated. The adequacy of this model for studies of morphological and functional regularities is verified. This model can be used for the development of a new concept of evaluation of thrombotic complications of mechanical injury.


Subject(s)
Hyperhomocysteinemia/pathology , Hyperhomocysteinemia/physiopathology , Microcirculation/physiology , Animals , Disease Models, Animal , Genotype , Hyperhomocysteinemia/genetics , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , Polymorphism, Single Nucleotide/genetics , Rats , Thrombosis/genetics , Thrombosis/physiopathology
5.
Urologiia ; (4): 154-160, 2018 Oct.
Article in Russian | MEDLINE | ID: mdl-30761807

ABSTRACT

The article presents pooled results of domestic and international studies investigating genetic aspects of urolithiasis associated with impaired calcium metabolism. The review highlights the importance of early and accurate diagnosis of hereditary diseases associated with kidney stone formation. Of more than 80 currently known monogenic forms of urolithiasis, the authors provide the list of the most significant forms. Using such molecular genetic methods as NGS (next generation sequencing) allows accurate detection of the genetic cause of the disease, develop an individual approach the patients management and timely prevention of the disease among the relatives of the proband.


Subject(s)
Urinary Calculi , Urolithiasis , Calcium , Humans
6.
Eksp Klin Gastroenterol ; (5): 58-64, 2016.
Article in Russian | MEDLINE | ID: mdl-28614646

ABSTRACT

The review presents an analysis of current data on the epidemiology, etiology, clinical and genetic characteristics of congenital anorectal malformations (AM). According to international registers of congenital malformations prevalence of the AM varies from 2 to 5 per 10,000 births. There was no change in the prevalence over time of AM (absence of temporal trends). Most studies have indicated the predominance of males among patients with AM. Approximately 40 - 70% of patients with AM have congenital malformations of other organs and systems. The data on the participation of genetic and environmental factors in the origin of the AM. A brief clinical and genetic characteristics of the most common syndromes (association) with the AM.


Subject(s)
Abnormalities, Multiple , Anorectal Malformations , Abnormalities, Multiple/epidemiology , Abnormalities, Multiple/etiology , Abnormalities, Multiple/genetics , Anorectal Malformations/epidemiology , Anorectal Malformations/etiology , Anorectal Malformations/genetics , Female , Humans , Male , Prevalence , Sex Factors
7.
Urologiia ; (2 Suppl 2): 95-102, 2016 Apr.
Article in Russian | MEDLINE | ID: mdl-28247651

ABSTRACT

The article presents summarized results of domestic and international studies of the genetic aspects of urolithiasis. The presented evidence suggests the importance of early and accurate molecular genetic diagnostics of hereditary diseases associated with stone formation for timely treatment and prevention for patients' relatives. Also provided are examples of using molecular genetic diagnostics in urologist's practice for monogenic and multifactorial diseases associated with stone formation. Taken together, these results show that using modern post-genomic technologies for assessing the risk of hereditary predisposition to urolithiasis is justified.


Subject(s)
Genetic Predisposition to Disease , Urolithiasis/genetics , Animals , Humans , Urolithiasis/metabolism
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