Candidate genes and single-nucleotide gene variants associated with muscle and tendon injuries in cyclic sports athletes

Sports injuries prevention is one of the key issues of the training process and reducing the risk of developing anxiety and depressive disorders in professional athletes. One of peculiarities of sports injuries is the loss of the ability to train in view of the tendon-ligamentous apparatus integrity, joints, muscles or bones violation. In cyclic sports, the most common are injuries to the ankle joint, injuries to muscles and tendons, and sprains. Injuries to ligaments and tendons are the result of multifactorial problems, including the discrepancy between training effects and the genetically determined capabilities of the athlete's body. Sports injuries consequences are determined by complex interactions between the athlete's genotype and environmental factors, in particular training influences. (1) Background: to review scientific articles on the problem of research on candidate genes and single-nucleotide variants (SNVs) of genes associated with muscle, tendon, and ligament injuries in cyclic sports athletes. (2) Methods: a search of articles for the period from 2008 to 2020 was conducted in the databases e-LIBRARY, SCOPUS, Web of Science, Google Scholar, Clinical keys, PubMed using the keywords: personalized medicine, genetics, candidate genes, single-nucleotide variant, polymorphism, muscle, tendon, injury, athlete. (3) Results: Studies have shown that muscle and tendon injuries in cyclical sports athletes are associated with SNV rs1800012, rs1107946 of the COL1A1 gene, SNV rs12722 of the COL5A1 gene, SNV rs679620 of the MMR3 gene, SNV rs2289360 of the ELN gene, SNV rs143383 of the GDF5 gene. The most studied polymorphisms are rs1800012, rs1107946 of the COL1A1 gene, rs12722 of the COL5A1 gene, and rs143383 of the GDF5 gene. The variable results of associative genetic studies and genome-wide studies are most likely due to the racial and ethnic heterogeneity of the samples and differences in the study design. (4) Conclusions: Identification of genetic markers associated with injuries and diseases of the musculoskeletal system, ligamentous apparatus, and the ability of tissue to regenerate can help sports doctors and coaches develop personalized strategies to prevent or reduce muscles, joints, and ligaments diseases in athletes. The translation of these research results into the training and treatment process is important for improving cyclic sports athletes' performance, reducing their professional mala-daptation and anxiety and depressive disorders development risk.

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Candidate genes associated with athletes' skeletal muscle functions regulation

Personalized Psychiatry and Neurology ◽

10.52667/2712-9179-2021-1-2-83-94 ◽

2021 ◽

Vol 1 (2) ◽

pp. 83-94

Author(s):

O. V. Balberova ◽

E. V. Bykov ◽

G. V. Medvedev

Keyword(s):

Candidate Genes ◽

Skeletal Muscles ◽

Sports Injuries ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Genetic Characteristics ◽

Endurance Strength ◽

Personalized Approach ◽

And Function ◽

Genetically Determined

It is generally recognized that an elite athlete's status is a multifactorial phenotype depending on many environmental and genetic factors. Variations in the sequence of nucleotides in deoxyribonucleic acid (DNA), in particular, single-nucleotide variants (SNVs) act as key internal factors associated with achieving high results in sports. The determination of specific individuals' genetic characteristics allows us to identify athletes who have the greatest genetically determined potential for certain sports that require speed, strength or endurance manifestation. Of course, peculiarities of the structure and function of skeletal muscles are among the most important characteristics in sports results context, in sports associated with the development of power / strength or endurance phenotypes. The composition and function of skeletal muscles are controlled by many different genes, and their SNVs can serve as strength or endurance athletes' status biomarkers. (1) Background: to conduct a thematic review of candidate genes studies and their single-nucleotide variants (SNVs) associated with the functioning of skeletal muscles in athletes. (2) Methods: A search for articles for the period from 2010 to 2020 was conducted in the databases SCOPUS, Web of Science, Google Calendar, Clinical keys, PubMed, e-LIBRARY using keywords and their combinations; (3) Conclusions: The identification of genetic biomarkers associated with muscular system regulation can help neurologists, sports doctors and coaches in developing personalized strategies for selecting children, adolescents and young adults for endurance, strength and speed sports (for example, running short, medium or long distances). Such a personalized approach will increase sports performance and reduce the risk of sports injuries of the musculoskeletal system.

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The Phenolyzer Suite: Prioritizing the Candidate Genes Involved in Microtia

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489419840052 ◽

2019 ◽

Vol 128 (6) ◽

pp. 556-562 ◽

Cited By ~ 1

Author(s):

Huang Xin ◽

Wang Changchen ◽

Liu Lei ◽

Yang Meirong ◽

Zhang Ye ◽

...

Keyword(s):

Candidate Genes ◽

High Throughput ◽

Potential Candidate ◽

Single Nucleotide Variants ◽

Gene Score ◽

Single Nucleotide ◽

Research Directions ◽

Score System ◽

Pathogenic Genes ◽

First Time

Objective: Microtia is a congenital malformation of the external ear. Great progress about the genetic of microtia has been made in recent years. This article was to prioritize the potential candidate pathogenic genes of microtia based on existing studies and reports, with the purpose of narrowing the range of following study scientifically and quickly. Method: A computational tool called Phenolyzer (phenotype-based gene analyzer) was used to prioritize microtia genes. Microtia, as a query term, was input in the interface of Phenolyzer. After several steps, including disease match, gene query, gene score system, seed gene growth, and gene ranking, the final results about genetic information of microtia were provided. Then we tracked details of the top 10 genes ranked by Phenolyzer on the basis of previous reports. Results: We detected 10 348 genes associated with microtia or related syndromes, and 78 genes of those genes belonged to seed genes. Every gene was given a score, and the gene with higher scores was more likely influence microtia. The top 10 ranked genes included HOXA2, CHD7, CDT1, ORC1, ORC4, ORC6, CDC6, MED12, TWIST1, and GLI3. Otherwise, four gene-gene interactions were displayed. Conclusion: This article prioritized candidate genes of microtia for the first time. High-throughput methods provide tens of thousands of single-nucleotide variants, indels, and structural variants, and only a handful are relevant to microtia or associated syndromes. Combine the ranked potential pathogenic genes list from Phenolyzer with the results of samples provided by high-throughput methods, and more precise research directions are presented.

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A Review of Epigenetics of PTSD in Comorbid Psychiatric Conditions

Genes ◽

10.3390/genes10020140 ◽

2019 ◽

Vol 10 (2) ◽

pp. 140 ◽

Cited By ~ 9

Author(s):

Caren J. Blacker ◽

Mark A. Frye ◽

Eva Morava-Kozicz ◽

Tamas Kozicz ◽

Marin Veldic

Keyword(s):

Psychiatric Disorder ◽

Candidate Genes ◽

Epigenetic Regulation ◽

Depressive Disorders ◽

Psychotic Disorders ◽

Psychological Symptoms ◽

Epigenetic Variation ◽

Post Traumatic Stress ◽

Childhood Experiences ◽

Complex Interactions

Post-traumatic stress disorder (PTSD) is an acquired psychiatric disorder with functionally impairing physiological and psychological symptoms following a traumatic exposure. Genetic, epigenetic, and environmental factors act together to determine both an individual’s susceptibility to PTSD and its clinical phenotype. In this literature review, we briefly review the candidate genes that have been implicated in the development and severity of the PTSD phenotype. We discuss the importance of the epigenetic regulation of these candidate genes. We review the general epigenetic mechanisms that are currently understood, with examples of each in the PTSD phenotype. Our focus then turns to studies that have examined PTSD in the context of comorbid psychiatric disorders or associated social and behavioral stressors. We examine the epigenetic variation in cases or models of PTSD with comorbid depressive disorders, anxiety disorders, psychotic disorders, and substance use disorders. We reviewed the literature that has explored epigenetic regulation in PTSD in adverse childhood experiences and suicide phenotypes. Finally, we review some of the information available from studies of the transgenerational transmission of epigenetic variation in maternal cases of PTSD. We discuss areas pertinent for future study to further elucidate the complex interactions between epigenetic modifications and this complex psychiatric disorder.

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Promising areas of research on the pharmacogenetics of dabigatran etexilate

Pharmacogenetics and Pharmacogenomics ◽

10.37489/2588-0527-2020-1-35-41 ◽

2020 ◽

pp. 35-41

Author(s):

A. V. Savinova ◽

N. A. Shnayder ◽

M. M. Petrova ◽

R. F. Nasyrova

Keyword(s):

Candidate Genes ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

P Glycoprotein ◽

Udp Glucuronosyltransferase

Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of promising areas of associated researches of SNV of genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.

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Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer's Disease based on the analysis of multi-omics data

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2021.07.010 ◽

2021 ◽

Author(s):

Shishi Min ◽

Zongchang Li ◽

Annie Shieh ◽

Gina Giase ◽

Riyue Bao ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Candidate Genes ◽

Late Onset ◽

Omics Data ◽

Single Nucleotide Variants ◽

Sporadic Alzheimer’S Disease ◽

Single Nucleotide

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Next generation sequencing analysis of patients with familial cervical artery dissection

European Stroke Journal ◽

10.1177/2396987317693402 ◽

2017 ◽

Vol 2 (2) ◽

pp. 137-143 ◽

Cited By ~ 11

Author(s):

Caspar Grond-Ginsbach ◽

Tobias Brandt ◽

Manja Kloss ◽

Suna Su Aksay ◽

Philipp Lyrer ◽

...

Keyword(s):

Connective Tissue ◽

Candidate Genes ◽

Allele Frequency ◽

Artery Dissection ◽

Cervical Artery Dissection ◽

Connective Tissue Disorders ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Cervical Artery ◽

Stop Loss

Background The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. Patients and methods Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as “benign” or “likely benign” in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database ( n = 33,370). Results Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8–52.9). Conclusion Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

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Pharmacokinetics and Pharmacogenetics of Apixaban

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2020-10-17 ◽

2020 ◽

Vol 16 (5) ◽

pp. 852-860

Author(s):

A. V. Savinova ◽

M. M. Petrova ◽

N. A. Shnayder ◽

E. N. Bochanova ◽

R. F. Nasyrova

Keyword(s):

Candidate Genes ◽

Factor Xa ◽

Potential Candidate ◽

Beta Oxidation ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Vein Thrombosis ◽

Genes Encoding ◽

Deep Vein

Apixaban is oral anticoagulant, it is widely used in prevention of stroke in non-valvular atrial fibrillation and treatment of deep vein thrombosis and pulmonary embolism. Its main mechanism of action is through reversible inhibition of factor Xa. It specifically binds and inhibits both free and bound factor Xa which ultimately results in reduction in the levels of thrombin formation. Apixaban is mainly metabolized by CYP3A4 with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP2J2 isoenzymes. Some of the major metabolic pathways of apixaban include o-demethylation, hydroxylation, and sulfation, with o-demethylapixabansulphate being the major metabolite. The aim of this review is analysis of associated researches of single nucleotide variants (SNV) of CYP3A5 and SULT1A1 genes and search for new candidate genes reflecting effectiveness and safety of apixaban. The search for full-text publications in Russian and English languages containing key words “apixaban”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of apixaban are considered in this review. The hypothesis about CYP и SULT1A enzymes influence on apixaban metabolism was examined. To date, numerous SNVs of the CYP3A5 and SULT1A1 genes have been identified, but their potential influence on pharmacokinetics apixaban in clinical practice needs to be further studies. The role of SNVs of other genes encoding beta-oxidation enzymes of apixaban (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2J2) and transporter proteins (ABCB1, ABCG2) in its efficacy and safety are not well understood, and ABCB1 and ABCG2 genes may be potential candidate genes for studies of the drug safety.

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Candidate Genes of Regulation of Skeletal Muscle Energy Metabolism in Athletes

Genes ◽

10.3390/genes12111682 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1682

Author(s):

Olga V. Balberova ◽

Evgeny V. Bykov ◽

German V. Medvedev ◽

Margarita A. Zhogina ◽

Kirill V. Petrov ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Candidate Genes ◽

Sports Performance ◽

Single Nucleotide Variants ◽

Long Distance ◽

Single Nucleotide ◽

Endurance Strength ◽

Muscle Energy ◽

Muscle Energy Metabolism

All biological processes associated with high sports performance, including energy metabolism, are influenced by genetics. DNA sequence variations in such genes, single nucleotide variants (SNVs), could confer genetic advantages that can be exploited to achieve optimal athletic performance. Ignorance of these features can create genetic “barriers” that prevent professional athletes from pursuing a career in sports. Predictive Genomic DNA Profiling reveals single nucleotide variations (SNV) that may be associated with better suitability for endurance, strength and speed sports. (1) Background: To conduct a research on candidate genes associated with regulation of skeletal muscle energy metabolism among athletes. (2) Methods: We have searched for articles in SCOPUS, Web of Science, Google Scholar, Clinical keys, PubMed, e-LIBRARY databases for the period of 2010–2020 using keywords and keywords combinations; (4) Conclusions: Identification of genetic markers associated with the regulation of energy metabolism in skeletal muscles can help sports physicians and coaches develop personalized strategies for selecting children, teenagers and young adults for endurance, strength and speed sports (such as jogging, middle or long distance runs). However, the multifactorial aspect of sport performances, including impact of genetics, epigenetics, environment (training and etc.), is important for personalized strategies for selecting of athletes. This approach could improve sports performance and reduce the risk of sports injuries to the musculoskeletal system.

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Candidate genes involved in the development of antipsychotic-induced tardive dyskinesia in patients with schizophrenia

Neuromuscular Diseases ◽

10.17650/2222-8721-2020-10-3-10-26 ◽

2020 ◽

Vol 10 (3) ◽

pp. 10-26

Author(s):

E. E. Vaiman ◽

N. A. Shnayder ◽

N. G. Neznanov ◽

R. F. Nasyrova

Keyword(s):

Tardive Dyskinesia ◽

Candidate Genes ◽

Side Reaction ◽

Single Nucleotide Variants ◽

Antipsychotic Therapy ◽

Drug Induced ◽

Single Nucleotide ◽

Genetic Characteristics ◽

Genes Encoding ◽

Undesirable Side Reaction

Introduction. Drug-induced dyskinesia is an iatrogenic undesirable side reaction from the extrapyramidal system that occurs during the administration of drugs, most often antipsychotics in patients with schizophrenia. At the end of the 20 th century, studies were conducted on the search for candidate genes and the carriage of single nucleotide variants of antipsychotics-induced tardive dyskinesia. Purpose of the study – to analyze research results reflecting candidate genes and their single nucleotide variants associated with antipsychotic-induced tardive dyskinesia. Materials and methods. We searched for full-text publications in Russian and English in the eLIBRARY, PubMed, Web of Science, Springer databases using keywords (tardive dyskinesia, drug-induced tardive dyskinesia, antipsychotics, antipsychotics, typical antipsychotics, atypical antipsychotics, genes, polymorphisms) and combined searches for words over the past decade. Results. The lecture discusses candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of antipsychotics Conclusion. Timely identification of individual genetic characteristics of the patient can contribute to the development of diagnostic test systems and in the future selection of the safest and most effective antipsychotic therapy.

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