scholarly journals The role of genetic polymorphism in the formation of atherosclerosis in the vessels of lower extremities

2012 ◽  
Vol 93 (3) ◽  
pp. 513-516
Author(s):  
M N Katina ◽  
R F Gayfullina ◽  
V V Valiullin ◽  
A A Rizvanov ◽  
R F Khamitov ◽  
...  
Keyword(s):  
Human Genome ◽  
Literature Search ◽  
Lower Extremities ◽  
Disease Course ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Genes ◽  
Genomics And Proteomics ◽  
The Individual

Personalized medicine involves the use of methods of genomics and proteomics by physicians for early diagnosis, prediction of the nature of the disease course and the choice of medicines and their doses based on personalized characteristics of the individual patient. Advances in the study of the human genome make it possible to reveal the interrelation between the individual mutations in the human genes (polymorphisms) and predisposition to certain diseases. Currently there are more than 10 million single-nucleotide polymorphisms in the human genome, however their biological role remains poorly understood. On the basis of a literature search of electronic full-text and abstract-only versions of articles, which was conducted in the PUBMED, OMIM and GENE databases, collected was the information on genetic predisposition to systemic atherosclerosis. The review is dedicated to polymorphisms of the major genes that play a role in the pathophysiology of atherosclerosis of the lower extremities.

scholarly journals Pathogenesis of atherosclerosis of arteries of the lower extremities: candidate genes and their polymorphism

2012 ◽  
Vol 93 (2) ◽  
pp. 311-314
Author(s):  
M N Katina ◽  
R F Gayfullina ◽  
V V Valiullin ◽  
A A Rizvanov
Keyword(s):  
Personalized Medicine ◽  
Early Diagnosis ◽  
Human Genome ◽  
Literature Search ◽  
Lower Extremities ◽  
Disease Course ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Genes ◽  
The Individual

Personalized medicine involves the use of genetic methods by physicians for early diagnosis, prediction of the nature of the disease course and the choice of medicines and their doses based on personalized characteristics of the individual patient. Advances in the study of the human genome make it possible to reveal the interrelation between different varieties of alleles of human genes (polymorphism) and predisposition to certain diseases. Currently there are more than 10 million single-nucleotide polymorphisms in the human genome, but their biological role remains poorly understood. On the basis of a literature search of electronic full-text and abstract-only versions of articles’, which was conducted in the PUBMED, OMIM and GENE databases, collected was the information on genetic predisposition to systemic atherosclerosis. The review is dedicated to polymorphisms of the major genes that play a role in the pathophysiology of atherosclerosis of the lower extremities.

scholarly journals From Single Variants to Protein Cascades

2015 ◽  
Vol 291 (4) ◽  
pp. 1582-1590
Author(s):  
Sabine C. Mueller ◽  
Björn Sommer ◽  
Christina Backes ◽  
Jan Haas ◽  
Benjamin Meder ◽  
...  
Keyword(s):  
Single Nucleotide Variants ◽  
Data Set ◽  
Single Nucleotide ◽  
Coding Regions ◽  
Healthy Humans ◽  
Cardiac Phenotype ◽  
Human Genes ◽  
Binding Pockets ◽  
The Individual

Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes. We developed a multiscale pipeline to systematically analyze the existence of quantitative effects of multiple nsSNVs and gene combinations in single individuals on pathogenicity. Based on this pipeline, we detected in a data set of 842 nsSNVs discovered in 76 genes related to cardiomyopathies, associated nsSNV combinations in seven genes present in at least 70% of all 639 patient samples, but not in a control cohort of healthy humans. Structural analyses of these revealed primarily an influence on the protein stability. For amino acid substitutions located at the protein surface, we generally observed a proximity to putative binding pockets. To computationally analyze cumulative effects and their impact, pathogenicity methods are currently being developed. Our approach supports this process, as shown on the example of a cardiac phenotype but can be likewise applied to other diseases such as cancer.

scholarly journals Using human demographic history to infer natural selection reveals contrasting patterns on different families of immune genes

2010 ◽  
Vol 278 (1711) ◽  
pp. 1587-1594 ◽  
Author(s):  
William Amos ◽  
Clare Bryant
Keyword(s):  
Natural Selection ◽  
Human Genome ◽  
Demographic History ◽  
Time Interval ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Immune Genes ◽  
Geographical Patterns ◽  
Human Genes ◽  
The Relationship

Detecting regions of the human genome that are, or have been, influenced by natural selection remains an important goal for geneticists. Many methods are used to infer selection, but there is a general reliance on an accurate understanding of how mutation and recombination events are distributed, and the well-known link between these processes and their evolutionary transience introduces uncertainty into inferences. Here, we present and apply two new, independent approaches; one based on single nucleotide polymorphisms (SNPs) that exploits geographical patterns in how humans lost variability as we colonized the world, the other based on the relationship between microsatellite repeat number and heterozygosity. We show that the two methods give concordant results. Of these, the SNP-based method is both widely applicable and detects selection over a well-defined time interval, the last 50 000 years. Analysis of all human genes by their Gene Ontology codes reveals how accelerated and decelerated loss of variability are both preferentially associated with immune genes. Applied to 168 immune genes used as the focus of a previous study, we show that members of the same gene family tend to yield similar indices of selection, even when located on different chromosomes. We hope our approach will provide a useful tool with which to infer where selection has acted to shape the human genome.

scholarly journals Synonymous SNP: Rare versus frequent codon can cause Phenotypic changes in the human genome

2019 ◽  
Author(s):  
Ashu Srivastav
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Human Genome ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Phenotypic Effect ◽  
Single Nucleotide ◽  
Coding Sequences ◽  
Phenotypic Changes ◽  
Genome Variability ◽  
The Individual

ABSTRACTSince the initial sequencing of the human genome, many projects are underway to understand the effects of genetic variation and phenotypic changes between individuals. Single nucleotide polymorphisms (SNPs) are an increasingly important tool for genetic and biomedical research. Synonymous Single Nucleotide Polymorphisms (sSNP) is an important source of human genome variability. It does not produce altered coding sequences therefore expected not to change the function of protein in which they occur. Examination of synonymous SNPs that change a rarely used codon into a frequently used one or vice versa may help in predicting their phenotypic effect on the individual carrying the change. Detail information of Human Synonymous Single-nucleotide-polymorphism may accelerate the research of personalized medicine since it has the crucial impact in the field of non-synonymous SNP.

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

scholarly journals The role of 25-hydroxyvitamin-D3 and vitamin D receptor gene in human periodontal ligament fibroblasts as response to orthodontic compressive strain: an in vitro study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Erika Calvano Küchler ◽  
Agnes Schröder ◽  
Vinicius Broska Teodoro ◽  
Ute Nazet ◽  
Rafaela Scariot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Single Nucleotide Polymorphisms ◽  
Periodontal Ligament ◽  
Compressive Strain ◽  
Nucleotide Polymorphisms ◽  
Periodontal Ligament Fibroblasts ◽  
Single Nucleotide ◽  
Cox 2

Abstract Background This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. Methods A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. Results RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05). Conclusions Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

scholarly journals NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

2010 ◽  
Vol 70 (4) ◽  
pp. 668-674 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Systemic Sclerosis ◽  
Potential Role ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Fibrosing Alveolitis ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

scholarly journals Type 2 Diabetes (T2D) Associated Polymorphisms Regulate Expression of Adjacent Transcripts in Transformed Lymphocytes, Adipose, and Muscle from Caucasian and African-American Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. E394-E403 ◽  
Author(s):  
Neeraj K. Sharma ◽  
Kurt A. Langberg ◽  
Ashis K. Mondal ◽  
Steven C. Elbein ◽  
Swapan K. Das
Keyword(s):  
Genome Wide Association ◽  
Small Subset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Allelic Expression Imbalance ◽  
Single Nucleotide ◽  
Metabolic Traits ◽  
Genome Wide

abstract Context: Genome-wide association scans (GWAS) have identified novel single nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated the role of nearby genes in T2D pathogenesis. Objective: We hypothesized that T2D-associated SNPs act as cis-regulators of nearby genes in human tissues and that expression of these transcripts may correlate with metabolic traits, including insulin sensitivity (SI). Design, Settings, and Patients: Association of SNPs with the expression of their nearest transcripts was tested in adipose and muscle from 168 healthy individuals who spanned a broad range of SI and body mass index (BMI) and in transformed lymphocytes (TLs). We tested correlations between the expression of these transcripts in adipose and muscle with metabolic traits. Utilizing allelic expression imbalance (AEI) analysis we examined the presence of other cis-regulators for those transcripts in TLs. Results: SNP rs9472138 was significantly (P = 0.037) associated with the expression of VEGFA in TLs while rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027) and adipose (P = 0.018). Significant association was also observed for rs17036101 (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS-implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r = −0.305) and SI (r = 0.230). Although only a minority of the T2D-associated SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated presence of other cis-regulatory polymorphisms in 54% of these transcripts. Conclusions: Our study suggests that a small subset of GWAS-identified SNPs may increase T2D susceptibility by modulating expression of nearby transcripts in adipose or muscle.

scholarly journals Associations between neurochemical receptor genes, 2D:4D, impulsivity and relationship quality

2018 ◽  
Vol 14 (12) ◽  
pp. 20180642 ◽  
Author(s):  
Eiluned Pearce ◽  
Rafael Wlodarski ◽  
Anna Machin ◽  
Robin I. M. Dunbar
Keyword(s):  
Relationship Quality ◽  
Multiple Testing ◽  
Romantic Relationship ◽  
Preliminary Evidence ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Digit Ratios ◽  
The Relationship ◽  
Romantic Relationship Quality

The ratio between the second and fourth digits (2D:4D) has been widely used as a proxy for fetal exposure to androgens and has been linked to a number of sociosexual traits in humans. However, the role of genes in this equation remains unknown. Here ( N = 474), we test, firstly, for associations between 2D:4D and single-nucleotide polymorphisms (SNPs) in nine neurochemical receptor genes ( AR, OXTR, AVPR1A, OPRM1, DRD1/2, ANKK1, 5HTR1A/2A ), and secondly, whether digit ratios mediate the relationship between genetic variation and sociosexuality. We demonstrate significant associations between AR , OPRM1 and AVPR1A and 2D:4D. Moreover, mediation analysis indicates that, in women, AR and OPRM1 variation drives digit ratios, which are related positively to impulsivity and, for OPRM1 , negatively to romantic relationship quality. Although these findings are subject to multiple testing issues, this study provides preliminary evidence that in women genetic factors may affect both impulsivity and perceived relationship quality through influencing factors indexed by digit ratios.

scholarly journals Genetic Variants in JAK1 Gene and Susceptibility to Hepatitis C Viral Infection in Iraq

2016 ◽  
Vol 10 (1) ◽  
pp. 37-41
Author(s):  
Fatima Abood Chaloob
Keyword(s):  
Hepatitis C ◽  
Hcv Infection ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Global Challenge ◽  
Pcr Products ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Apparently Healthy

Infection with hepatitis C virus (HCV) imposes a global challenge with over 180 million cases worldwide. Only few patients spontaneously had their virus neutralized, while most patients develop chronic HCV infection. This implies a key role of genetic factors in viral clearance or persistence. The current study aimed at clarifying the effect of certain single nucleotide polymorphisms (SNPs) on individual's susceptibility to HCV infection.  A total of 60 patients with confirmed HCV infection and 35 apparently healthy individuals were enrolled in this study. Blood sample was obtained from each participant, from which DNA was extracted. The JAK1gene was amplified with conventional PCR technique using three sets of primers targeting three SNPs in this gene: rs2780895, rs4244165 and rs17127024. Restriction fragment length polymorphism (RFLP) was used for genotyping of PCR products. Each of rs2780895 and rs17127024 had two genotypes in both patients and controls, however, only the heterozygous genotype of the SNP rs2780895 (CT) significantly associated with the susceptibility to HCV. The SNP rs4244165 appeared in only with homozygous wild genotype (GG) in both patients and controls. It can be concluded that allele T of the SNP rs2780895 could be considered as a risk factor for infection with HCV

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