-
Biotechnology Advances Oct 2023Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves... (Review)
Review
Temperature affects cellular processes at different spatiotemporal scales, and identifying the genetic and molecular mechanisms underlying temperature responses paves the way to develop approaches for mitigating the effects of future climate scenarios. A systems view of the effects of temperature on cellular physiology can be obtained by focusing on metabolism since: (i) its functions depend on transcription and translation and (ii) its outcomes support organisms' development, growth, and reproduction. Here we provide a systematic review of modelling efforts directed at investigating temperature effects on properties of single biochemical reactions, system-level traits, metabolic subsystems, and whole-cell metabolism across different prokaryotes and eukaryotes. We compare and contrast computational approaches and theories that facilitate modelling of temperature effects on key properties of enzymes and their consideration in constraint-based as well as kinetic models of metabolism. In addition, we provide a summary of insights from computational approaches, facilitating integration of omics data from temperature-modulated experiments with models of metabolic networks, and review the resulting biotechnological applications. Lastly, we provide a perspective on how different types of metabolic modelling can profit from developments in machine learning and models of different cellular layers to improve model-driven insights into the effects of temperature relevant for biotechnological applications.
Topics: Temperature; Metabolic Networks and Pathways; Phenotype; Models, Biological
PubMed: 37348662
DOI: 10.1016/j.biotechadv.2023.108203 -
Brazilian Oral Research Jun 2017Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions... (Review)
Review
Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.
Topics: DMF Index; Dental Caries; Dental Caries Susceptibility; Female; Genetic Association Studies; Genetic Markers; Humans; Male; Polymorphism, Genetic; Risk Factors; Salivary Proteins and Peptides
PubMed: 28591238
DOI: 10.1590/1807-3107BOR-2017.vol31.0041 -
European Journal of Obstetrics,... Dec 2022We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also focusing on temporal trends of the condition, to compare the PCOS prevalence among populations with a similar level of diagnostic resources availability and attitudes toward health problems, to improve comparability of estimates. We considered Europe and USA, two high-income areas with these characteristics. The overall PCOS prevalence according to the NIH1990, ESHRE/ASRM 2003, AES-PCOS diagnostic criteria was respectively 6.2 % (95%CI 5.3-7.0), 19.5 % (95%CI 17.3-21.6), and 15.0 % (95%CI 12.9-17.1), with no appreciable heterogeneity across geographic areas. Phenotype A, the "complete PCOS", showed higher prevalence in all areas (44.8%, 95%CI 40.3-49.3), followed by phenotype D, called "non-hyperandrogenic PCOS" (19.5%), phenotype C termed as "ovulatory PCOS" (16.2%), and phenotype B, presenting as phenotype A but without polycystic ovarian morphology (14.9%). In all the studies analysing temporal trends of PCOS, an increase in prevalence of PCOS was reported, due, at least in part, to changing diagnostic criteria. The prevalence of PCOS is similar in European countries and the USA. Interestingly, some differences in the frequency of PCOS phenotypes emerged between the two areas with a higher frequency of phenotype A and a lower one of phenotype C in the USA. Recognizing the factors which explain these differences would lead to a better understanding of the etiopathogenesis and the clinical expression of PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Prevalence; Europe; Phenotype
PubMed: 36343588
DOI: 10.1016/j.ejogrb.2022.10.020 -
BMC Oral Health Jan 2024Periodontal phenotype is regarded to be one of the key factors influencing the efficacy of restorative therapies in dental practice. The objective of the systematic...
BACKGROUND
Periodontal phenotype is regarded to be one of the key factors influencing the efficacy of restorative therapies in dental practice. The objective of the systematic review was to explore the importance of thin and thick periodontal phenotypes and how they affect the outcome of periodontal and restorative therapies by looking at a number of academic publications from various online databases.
METHODS
Following the PRISMA guidelines (Preferred Reporting Items for Systematic Review standards), relevant data will be searched and retrieved from three significant scientific databases, including PubMed, EBSCO, and Scopus. The articles with full texts that matched the keywords and published in English between 2018 and 2023 were taken into consideration.
RESULTS
The majorities of these articles were based on the type of periodontal phenotype and their impact on periodontal and restorative treatment outcomes were selected. The initial search yielded a total of 530 articles. Only 273 were relevant to the review's objectives, and these were considered for determining eligibility. Only 20 publications were eligible for analysis.
CONCLUSION
Understanding these anatomical aspects of periodontal phenotype is crucial to both periodontology and restorative dentistry. The clinical outcome of restorative, prosthetic, orthodontic, surgical, and periodontal therapies is determined in large part by the periodontal phenotype, which also plays a significant role in clinical failure or success in dental treatments.
TRIAL REGISTRATION
This study protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO) dated 16th June 2023 with the registration ID CRD42023432568.
Topics: Humans; Periodontics; Dental Care; Databases, Factual; Phenotype
PubMed: 38191372
DOI: 10.1186/s12903-023-03777-3 -
Journal of Pediatric Gastroenterology... May 2022The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms...
BACKGROUND AND AIMS
The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease.
METHODS
Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored.
RESULTS
One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores.
CONCLUSIONS
Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.
Topics: Abnormalities, Multiple; Actins; Colon; Female; Humans; Intestinal Pseudo-Obstruction; Male; Phenotype; Pregnancy; Urinary Bladder
PubMed: 35149643
DOI: 10.1097/MPG.0000000000003400 -
Journal of Autoimmunity Sep 2017With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs.... (Review)
Review
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated non-coding RNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that are affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomics and epigenomics research in SSc.
Topics: Epigenomics; Gene-Environment Interaction; Genetic Predisposition to Disease; Genomics; HLA Antigens; Humans; Interferon Regulatory Factors; Polymorphism, Genetic; STAT4 Transcription Factor; Scleroderma, Systemic; Signal Transduction; Transforming Growth Factor beta
PubMed: 28526340
DOI: 10.1016/j.jaut.2017.05.004 -
Scientific Reports Mar 2022DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological... (Meta-Analysis)
Meta-Analysis
DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case-control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI) 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for liver cancer. All assays, except the homologous recombination repair assay, showed statistically significant associations with cancer. The effect size ranged from 1.90 (1.00, 3.60) for the etoposide-induced double-strand break assay to 5.06 (3.67, 6.99) for the γ-H2AX assay. The consistency and strength of the associations support the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding their use related to age and screening initiation.
Topics: Case-Control Studies; DNA Repair; Humans; Phenotype; Prospective Studies; Skin Neoplasms
PubMed: 35233009
DOI: 10.1038/s41598-022-07256-7 -
Genes Oct 2021Suicide behavior (SB) has been highly associated with the response to stress and the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to summarize... (Review)
Review
BACKGROUND
Suicide behavior (SB) has been highly associated with the response to stress and the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to summarize the results obtained in genetic studies that analyzed the HPA axis-stress pathway and SB through a systematic review.
METHODS
We performed an online search in PubMed, EBSCO, Web of Science, Scopus, and PsycoInfo databases up to May 2021. We followed the PRISMA guidelines for systematic reviews. We included case-control and expression studies that provided data on mRNA expression and single-nucleotide polymorphisms of genes associated with SB.
RESULTS
A total of 21,926 individuals participated across 41 studies (not repeats); 34 studies provided data on single-nucleotide polymorphisms in 21,284 participants and 11 studies reported data on mRNA expression in 1034 participants. Ten genes were identified: , , , , , , , , and .
CONCLUSIONS
Our findings suggest that key stress pathway genes are significantly associated with SB and show potential as biomarkers for SB.
Topics: Gene Expression Regulation; Gene-Environment Interaction; Genetic Association Studies; Humans; Hypothalamo-Hypophyseal System; Polymorphism, Single Nucleotide; Stress, Psychological; Suicide; Suicide Prevention
PubMed: 34681002
DOI: 10.3390/genes12101608 -
Clinical Epigenetics Apr 2019Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk.
METHODS
A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality.
RESULTS
Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality.
CONCLUSION
Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Humans; Mortality
PubMed: 30975202
DOI: 10.1186/s13148-019-0656-7 -
Diabetologia Aug 2023To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death. (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.
METHODS
This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach.
RESULTS
A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA (53-75 mmol/mol [7-9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×10/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19 vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out.
CONCLUSIONS/INTERPRETATION
Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease.
REGISTRATION
PROSPERO registration no. CRD42020193692.
PREVIOUS VERSION
This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 FUNDING: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).
Topics: Male; Humans; COVID-19; SARS-CoV-2; Diabetes Mellitus; Prognosis; Phenotype; Observational Studies as Topic
PubMed: 37204441
DOI: 10.1007/s00125-023-05928-1