scholarly journals The role of the p53 tumor suppressor in metabolism and diabetes

2016 ◽  
Vol 231 (2) ◽  
pp. R61-R75 ◽  
Author(s):  
Che-Pei Kung ◽  
Maureen E Murphy
Keyword(s):  
Tumor Suppression ◽  
Metabolic Diseases ◽  
Nucleotide Polymorphisms ◽  
Review Of The Literature ◽  
Single Nucleotide ◽  
Cycle Arrest ◽  
Transcription Factor P53 ◽  
The Impact ◽  
The Relationship

In the context of tumor suppression, p53 is an undisputedly critical protein. Functioning primarily as a transcription factor, p53 helps fend off the initiation and progression of tumors by inducing cell cycle arrest, senescence or programmed cell death (apoptosis) in cells at the earliest stages of precancerous development. Compelling evidence, however, suggests that p53 is involved in other aspects of human physiology, including metabolism. Indeed, recent studies suggest that p53 plays a significant role in the development of metabolic diseases, including diabetes, and further that p53’s role in metabolism may also be consequential to tumor suppression. Here, we present a review of the literature on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis and insulin resistance. Additionally, we discuss the emerging role of genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the impact of p53 in metabolic disease and diabetes. A better understanding of the relationship between p53, metabolism and diabetes may one day better inform the existing and prospective therapeutic strategies to combat this rapidly growing epidemic.

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 Association of the polymorphism of the vitamin D receptor gene (VDR) with the risk of leprosy in the Brazilian Amazon

2021 ◽  
Author(s):  
Jasna Letícia Pinto Paz ◽  
Maria do Perpétuo Socorro Corrêa Amador Silvestre ◽  
Letícia Siqueira Moura ◽  
Ismari Perini Furlaneto ◽  
Yan Corrêa Rodrigues ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Genetic Factors ◽  
Receptor Gene ◽  
Mycobacterium Leprae ◽  
Nucleotide Polymorphisms ◽  
Vdr Gene ◽  
Single Nucleotide ◽  
The Relationship

The transmission and evolution of leprosy depends on several aspects, including immunological and genetic factors of the host, as well as genetic factors of Mycobacterium leprae. This study evaluated the association of single nucleotide polymorphisms (SNPs) on the FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) regions of the vitamin D receptor (VDR) gene with leprosy. A total of 405 individuals were evaluated, composed by groups of 100 multibacillary and 57 paucibacillary patients, and 248 healthy contacts. Blood samples were collected from patients and contacts. The genotyping was performed by sequencing of the interest regions. The alleles of the studied SNPs, and of SNP FokI genotypes, were not associated with leprosy. For the SNP on TaqI region, the relationship between the tt genotype, and for the SNP ApaI, the AA genotype, revealed an association with susceptibility to MB form, while Aa genotype with protection. The extended genotypes AaTT and AaTt of ApaI and TaqI were associated with protection to against MB form. Futher studies analyzing the expression of the VDR gene and the correlation with its SNPs might help to clarify the role of polymorphisms on the immune response in leprosy.

scholarly journals Hyperuricemia and chronic kidney disease

2021 ◽  
pp. 77-81
Author(s):  
Olga Kompaniets
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Clinical Studies ◽  
Review Of The Literature ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

The article is devoted to a review of the literature on the impact of hyperuricemia on the development and progression of chronic kidney disease (CKD). The tendency of changes of views on the role of uric acid in the pathogenesis of CKD is demonstrated. An analysis of experimental, epidemiological and clinical studies on the effects of uric acid on the physiology of the nephron and endothelial tissues, the relationship of hyperuricemia with metabolic and cardiorenal syndromes.

scholarly journals The role of polymorphic ERAP1 in autoinflammatory disease

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Emma Reeves ◽  
Edward James
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Autoinflammatory Disease ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Cell Functions ◽  
The Impact

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses. These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences. Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions. Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations. Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions. ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented. The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated. More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses. Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis.

Primer in Genetics and Genomics, Article 3–Explaining Human Diversity: The Role of DNA

2017 ◽  
Vol 19 (3) ◽  
pp. 350-356 ◽  
Author(s):  
Catherine Y. Read
Keyword(s):  
Deoxyribonucleic Acid ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Human Diversity ◽  
Single Nucleotide ◽  
Structural Alterations ◽  
Genetics And Genomics ◽  
Environmental Events ◽  
The Impact

Genetic variation lays the foundation for diversity and enables humans to adapt to changing environments. The order of the nucleotides adenine, guanine, cytosine, and thymine on the deoxyribonucleic acid (DNA) molecules of the nuclear chromosomes and mitochondrial DNA (mtDNA) plays an important role in normal cell division, tissue development, and reproduction but is susceptible to alteration from a large number of random, inherited, or environmental events. Variations can range from a change in a single nucleotide to duplication of entire chromosomes. Single nucleotide polymorphisms are the major source of human heterogeneity. Other variations that can alter phenotypes and adversely impact growth, development, and health include copy number variations, aneuploidies, and structural alterations such as deletions, translocations, inversions, duplications, insertions, or mutations in mtDNA. In addition, DNA rearrangements in somatic cells underlie the uncontrolled cell growth found in cancer. This article explores the mechanisms by which variations in DNA arise and the impact those changes can have on human health.

Role of rs10406069 in miR-5196 in hyperdiploid childhood acute lymphoblastic leukemia

Epigenomics ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 1949-1955
Author(s):  
Angela Gutierrez-Camino ◽  
Chantal Richer ◽  
Pascal St-Onge ◽  
Elixabet Lopez-Lopez ◽  
Ana Carbone Bañeres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mirna Genes ◽  
Relevant Role ◽  
The Impact

Aim: To determine the role of single nucleotide polymorphisms (SNPs) in noncoding RNAs in childhood acute lymphoblastic leukemia (ALL) subtypes. Materials & methods: We screened all SNPs in 130 pre-miRNA genes to assess their role in the susceptibility of the most common subtypes of ALL: hyperdiploid and ETV6-RUNX1. Results: In two independent cohorts, we found a significant association between rs10406069 in miR-5196 and the risk of developing hyperdiploid ALL. This observation could be explained by the impact of the SNP on miR-5196 expression and in turn, in its target genes. Indeed, rs10406069 was associated with expression changes in SMC1A, a gene involved in sister chromatin cohesion. Conclusion: rs10406069 in miR-5196 may have a relevant role in hyperdiploid ALL risk.

scholarly journals Association Between rs12037447, rs146732504, rs151078858, rs55723436, and rs6094136 Polymorphisms and Kawasaki Disease in the Population of Polish Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Piotr Buda ◽  
Maciej Chyb ◽  
Anna Smorczewska-Kiljan ◽  
Anna Wieteska-Klimczak ◽  
Agata Paczesna ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Developed Countries ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Coronary Artery Involvement ◽  
Genome Wide

Background: Kawasaki disease (KD) is an acute self-limited febrile vasculitis that mainly affects young children. Coronary artery involvement is the most serious complication in children with KD. It is currently the leading cause of acquired cardiac disease in children from developed countries. Literature data indicate a significant role of genetic susceptibility to KD.Objective: The aim of this study was to perform the first Genome-Wide Association Study (GWAS) in a population of Polish children with KD and identify susceptible genes involved in the pathogenesis of KD.Materials and Methods: The blood samples of Kawasaki disease patients (n = 119) were collected between 2016 and 2020, isolated and stored at the Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute in Warsaw. The control group was based on Polish donors (n = 6,071) registered as the POPULOUS collection at the Biobank Lab of The Department of Molecular Biophysics in University of Lodz. DNA samples were genotyped for 558,231 Single Nucleotide Polymorphisms (SNPs) using the 24 × 1 Infinium HTS Human Core Exome microarrays according to the protocol provided by the manufacturer. In order to discover and verify genetic risk-factors for KD, association analysis was carried out using PLINK 1.9.Results: Of all 164,395 variants, 5 were shown to occur statistically (padjusted < 0.05) more frequent in Kawasaki disease patients than in controls. Those are: rs12037447 in non-coding sequence (padjusted = 8.329 × 10−4, OR = 8.697, 95% CI; 3.629–20.84) and rs146732504 in KIF25 (padjusted = 0.007354, OR = 11.42, 95% CI; 3.79–34.43), rs151078858 in PTPRJ (padjusted = 0.04513, OR = 8.116, 95% CI; 3.134–21.01), rs55723436 in SPECC1L (padjusted = 0.04596, OR = 5.596, 95% CI; 2.669–11.74), rs6094136 in RPN2 (padjusted = 0.04755, OR = 10.08, 95% CI; 3.385–30.01) genes.Conclusion: Polymorphisms of genes KIF25, PTRPJ, SPECC1L, RNP2 may be linked with the incidence of Kawasaki disease in Polish children.

scholarly journals Role of IL-1β Mutation in Peri-implantitis: Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Irene Lafuente-Ibáñez de Mendoza ◽  
Amaia Setien-Olarra ◽  
Ana María García-de la Fuente ◽  
José Manuel Aguirre-Urizar ◽  
Xabier Marichalar-Mendia
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Inflammatory Protein ◽  
History Of ◽  
Implant Therapy ◽  
Plaque Control ◽  
The Relationship

Abstract Background: To perform a systematic review and meta-analysis on the presence of IL-1β polymorphisms in patients with peri-implantitis (PI). PI is the main complication associated to dental implant therapy. Although its main risk factors are history of periodontitis, poor plaque control and lack of regular maintenance, genetic susceptibility could also be a determinant factor for its appearance. Single nucleotide polymorphisms (SNP) are small mutations of the DNA, that alter the osseointegration of implants. Interleukin 1β (IL-1β) is an inflammatory protein that participates in both destruction of the extracellular matrix and reabsorption of the alveolar bone.Methods: A bibliographical research was made in PubMed, Scopus and Web of Science (keywords: "single nucleotide polymorphism", “polymorphism”, "periimplantitis", "SNP" and "implant failure"). Results: There is no significant relation between of IL-1β (+3953) SNP and PI, but there is a statistically significant association of peri-implant bone loss with the homozygotic model of IL-1β (-511) (I2=0%, p=0.555; OR: 2.255; IC: 1.040-4.889)Conclusions: Absence of a strong link between of IL-1β polymorphisms and PI must be taken with caution due to the heterogeneous methodological design, sample size and diagnostic criteria of the studies. Thus, more well-designed studies are needed, that analyse the relationship between IL-1β polymorphism and PI.

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