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International Journal of Molecular... Oct 2022Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to... (Review)
Review
Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to monitor recovery. Small non-coding RNAs (sncRNAs) including microRNAs can be measured in saliva following TBI and have been investigated as potential diagnostic markers. The aim of this systematic review was to investigate the diagnostic or prognostic ability of microRNAs extracted from saliva in human subjects. PubMed, Embase, Scopus, PsycINFO and Web of Science were searched for studies that examined the association of saliva microRNAs in TBI. Original studies of any design involving diagnostic capacity of salivary microRNAs for TBI were selected for data extraction. Nine studies met inclusion criteria, with a heterogeneous population involving athletes and hospital patients, children and adults. The studies identified a total of 188 differentially expressed microRNAs, with 30 detected in multiple studies. MicroRNAs in multiple studies involved expression change bidirectionality. The study design and methods involved significant heterogeneity that precluded meta-analysis. Early data indicates salivary microRNAs may assist with TBI diagnosis. Further research with consistent methods and larger patient populations is required to evaluate the diagnostic and prognostic potential of saliva microRNAs.
Topics: Adult; Child; Humans; MicroRNAs; Brain Injuries, Traumatic; Biomarkers; Saliva
PubMed: 36361944
DOI: 10.3390/ijms232113160 -
PloS One 2011Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex.
METHODOLOGY/PRINCIPAL FINDINGS
We searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions.
CONCLUSIONS
Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.
Topics: Animals; Cohort Studies; Gene Frequency; Genotype; Humans; Overweight; Polymorphism, Single Nucleotide; Receptors, Leptin
PubMed: 22028824
DOI: 10.1371/journal.pone.0026157 -
Medicine Oct 2016Between western European countries, the hepatitis C virus (HCV) endemic is highest in Italy. The main objective of this paper is to estimate the endemic diffusion of... (Meta-Analysis)
Meta-Analysis Review
Epidemiological burden estimates for pathologies with a nonconstant risk: an application to HCV in Italy according to age, Metavir score, and genotype: A systematic review and meta-analysis.
Between western European countries, the hepatitis C virus (HCV) endemic is highest in Italy. The main objective of this paper is to estimate the endemic diffusion of hepatitis C at the national level and by geographical area, with an extrapolation at the regional level and by uniform cohorts of subjects (by sex and year of birth). The secondary objective is a stratification by gravity of the estimated statistical figures to provide an overview of possible targets of the new anti-HCV treatments.PubMed and the Cochrane Library were searched for relevant Italian populations studies regarding HCV prevalence. Random and fixed effect models were used for pooling data. To develop the epidemiological model, a meta-analysis of studies of Italian populations and the explicit consideration of the changes in the etiology of the disease in different cohorts (by year of birth) of population and the impact of effective treatments that have been introduced since the 1990s. A Markovian transition model, which is based on the distribution of HCV+ and HCV Ribonucleic Acid (RNA)+ subjects, provides a plausible assessment of the Italian situation. The Meta-analysis of Observational Studies in Epidemiology recommendations/statements were followed.In 2014, 1569,215 HCV+ subjects (95% credible interval [CrI]: 1202,630-2021,261) were estimated in Italy, with a 2.58% prevalence (95% CrI: 1.98%-3.33%). A total of 828,884 HCV RNA+ subjects (95% CrI: 615,892-1081,123), which is equal to a 1.36% prevalence (95% CrI: 1.01%-1.78%), is higher in southern Italy and the islands (1.9%) than in central-northern Italy (1.1%). The predominance of adult and elderly subjects, with an old or very old infection, inevitably entails a significant number of HCV RNA+ subjects in the advanced stages of the illness. According to our estimates, approximately 400,000 subjects have cirrhosis, decompensated cirrhosis, and hepatocarcinoma, with a median age of 70 years.The model aims to support policymakers to define action plans by providing an estimate of both the emerged infected population and nonemerged infected population by age, gender, gravity, genotype, and geographical area. In the future, the model may contribute to simulation of the costs and outcome of different action strategies that can be adopted by health authorities.
Topics: Age Factors; Genotype; Hepacivirus; Hepatitis C; Humans; Incidence; Italy; Prevalence; RNA, Viral; Risk Factors
PubMed: 27759643
DOI: 10.1097/MD.0000000000005143 -
JCO Global Oncology Mar 2022Overexpression of the gene is significantly associated with different types of cancers, including breast cancer. In this study, the effects of single-nucleotide... (Meta-Analysis)
Meta-Analysis
PURPOSE
Overexpression of the gene is significantly associated with different types of cancers, including breast cancer. In this study, the effects of single-nucleotide polymorphisms rs11549465, rs11549467, and rs2057482 of the gene and their association with breast cancer were systematically investigated through meta-analysis.
MATERIALS AND METHODS
After a systematic review, nine case-control studies of the rs11549465 C/T polymorphism, six case-control studies of the rs11549467 G/A polymorphism, and one case-control study of the rs2057482 C/T polymorphism were included in this meta-analysis. The summary pooled odds ratios with 95% CIs were evaluated to detect the relationship between polymorphisms and breast cancer susceptibility.
RESULTS
Subgroup-stratified analyses showed that the T and TT genotypes of the rs11549465 C/T polymorphism were significantly associated with increased breast cancer risk in the Asian population under three genetic models (allele, homozygous, and recessive). rs11549467 G/A analyses indicated that the A and AA genotypes were significantly associated with increased breast cancer risk in the Asian population under allele and dominant models. However, no association with breast cancer was observed in the White population for the rs11549465 C/T and rs11549467 G/A polymorphisms. In addition, the rs2057482 C/T polymorphism showed no association with breast cancer under any genetic models or by ethnicity-stratified analyses.
CONCLUSION
The results of this meta-analysis suggested that the rs11549465 C/T and rs1154946 G/A polymorphisms were significantly associated with increased breast cancer risk in the Asian population, but no associations were found in the White population. Thus, could be an important biomarker for population-based breast cancer screening.
Topics: Breast Neoplasms; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Hypoxia; Polymorphism, Single Nucleotide
PubMed: 35507894
DOI: 10.1200/GO.21.00399 -
Cadernos de Saude Publica 2008The clinical and diagnostic aspects of cystic fibrosis have been extensively reviewed, with an emphasis on neonatal screening. This systematic literature review involved... (Review)
Review
The clinical and diagnostic aspects of cystic fibrosis have been extensively reviewed, with an emphasis on neonatal screening. This systematic literature review involved a search for relevant contributions in the PubMed and SciELO databases. The first references to cystic fibrosis date to the Middle Ages. Cystic fibrosis is the most frequent autosomal recessive hereditary disease among Caucasians (1:2,000 to 3,500). More than 1,000 mutations lead to the disease, the most common being "F508, with 70% prevalence among Canadian, Northern European, and American Caucasians and 23 to 55% prevalence among Brazilians. The basic defect is in chloride ion secretion. Cystic fibrosis screening has long been controversial, and after almost three decades, there are few nationwide programs (most are regional or local). However, the U.S. Centers for Disease Control and Prevention (CDC) has concluded that screening for cystic fibrosis is justified. The lack of a specific screening test and the ethnic heterogeneity of the Brazilian population pose challenges for neonatal screening.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Black People; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA; Humans; Immunohistochemistry; Incidence; Infant, Newborn; Lectins, C-Type; Neonatal Screening; Pancreatitis-Associated Proteins; Prenatal Diagnosis; Trypsin; United States; White People
PubMed: 18797725
DOI: 10.1590/s0102-311x2008001600002 -
PloS One 2017Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we... (Review)
Review
BACKGROUND
Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies.
METHODOLOGY
A systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.
RESULTS
Fifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.
CONCLUSIONS
Thus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.
PROSPERO REGISTRATION NUMBER
CRD42016036063.
Topics: Connexins; Databases, Factual; Genetic Association Studies; Humans; Myoclonic Epilepsy, Juvenile; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases; Receptors, Metabotropic Glutamate; Transcription Factors; Gap Junction delta-2 Protein
PubMed: 28636645
DOI: 10.1371/journal.pone.0179629 -
Human Genomics Mar 2021An increasing number of countries are investing efforts to exploit the human genome, in order to improve genetic diagnostics and to pave the way for the integration of... (Review)
Review
An increasing number of countries are investing efforts to exploit the human genome, in order to improve genetic diagnostics and to pave the way for the integration of precision medicine into health systems. The expected benefits include improved understanding of normal and pathological genomic variation, shorter time-to-diagnosis, cost-effective diagnostics, targeted prevention and treatment, and research advances.We review the 41 currently active individual national projects concerning their aims and scope, the number and age structure of included subjects, funding, data sharing goals and methods, and linkage with biobanks, medical data, and non-medical data (exposome). The main aims of ongoing projects were to determine normal genomic variation (90%), determine pathological genomic variation (rare disease, complex diseases, cancer, etc.) (71%), improve infrastructure (59%), and enable personalized medicine (37%). Numbers of subjects to be sequenced ranges substantially, from a hundred to over a million, representing in some cases a significant portion of the population. Approximately half of the projects report public funding, with the rest having various mixed or private funding arrangements. 90% of projects report data sharing (public, academic, and/or commercial with various levels of access) and plan on linking genomic data and medical data (78%), existing biobanks (44%), and/or non-medical data (24%) as the basis for enabling personal/precision medicine in the future.Our results show substantial diversity in the analysed categories of 41 ongoing national projects. The overview of current designs will hopefully inform national initiatives in designing new genomic projects and contribute to standardisation and international collaboration.
Topics: Genetic Diseases, Inborn; Genome, Human; Genomics; Humans; Information Dissemination; Neoplasms; Precision Medicine
PubMed: 33761998
DOI: 10.1186/s40246-021-00315-6 -
Medicine Dec 2014Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for... (Meta-Analysis)
Meta-Analysis Review
Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.
Topics: Amino Acid Substitution; Asian People; Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Liver Neoplasms; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein
PubMed: 25546681
DOI: 10.1097/MD.0000000000000330 -
Investigative Ophthalmology & Visual... Jul 2023The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a...
PURPOSE
The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a generalizable, worldwide prevalence figure could be proposed.
METHODS
Extensive literature search strategies were conducted, interrogating PubMed, Scopus, and Web of Science, to locate relevant literature. Ultimately 34 studies reporting original data were included for analysis.
RESULTS
Findings showed that most data were outdated, and only 6 of 34 articles (18%) were published after 2010. There were few good studies with sound methodology and large, clearly defined population samples. Only a small proportion of countries worldwide (26/193 [13%]) have produced prevalence figures for OCA. By continent, African studies were disproportionately represented (15/34 [44%]). The highest prevalence rates (range, 1 in 22 to 1 in 1300; mean, 1 in 464) were reported in population isolates. The mean prevalence from four African countries was 1 in 4264 (range, 1 in 1755 to 1 in 7900). Prevalence for three countries in Europe (mean, 1 in 12,000; range, 1 in 10,000 to 1 in 15,000) may be underestimated, as the phenotype, in fair-skinned populations, may be missed or misdiagnosed as ocular albinism or isolated visual impairment. Population rates may vary depending on local cultural factors (e.g., consanguineous matings) and may change over time.
CONCLUSIONS
The prevalence of OCA varies widely between continents and population groups, and it is often influenced by local factors. It was not possible, therefore, to determine a single, generalizable worldwide prevalence rate for OCA, although continental rates for Africa and Europe are useful.
Topics: Humans; Mutation; Prevalence; Albinism, Oculocutaneous; Phenotype; Albinism, Ocular
PubMed: 37440261
DOI: 10.1167/iovs.64.10.14 -
PloS One 2012Coronary artery disease (CAD) is the most common heart disease worldwide. Association of CAD with variants in the myocyte enhancer factor 2A (MEF2A) gene, the first... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coronary artery disease (CAD) is the most common heart disease worldwide. Association of CAD with variants in the myocyte enhancer factor 2A (MEF2A) gene, the first identified CAD-causing gene, has attracted special attention but the results are controversial. We aimed to evaluate this genetic association via a case-control study and meta-analysis.
METHODOLOGY/PRINCIPAL FINDINGS
We performed a case-control association study to investigate the relationship between variations in exon 11 of MEF2A gene and CAD in 1045 sporadic patients and 1008 controls enrolled angiographically among southern Chinese population, and then the data from this study were compared and discussed in a systematic review and meta-analysis with all available published studies on MEF2A gene and CAD. In total, eight variants were identified (21-bp deletion, CAG repeats, CCG repeats, a CCA deletion and four SNPs). No significant link was observed between the common (CAG)(n) polymorphism and CAD, whereas the rare 21-bp deletion was detected only in five affected individuals. The meta-analysis of (CAG)(n) polymorphism and CAD risk, including nine studies with 3801 CAD patients and 4020 controls, also provided no convincing evidence for the genetic association, even upon stratification by race (mainly Whites and Chinese). However, the 21-bp deletion was regarded as a potentially logical, albeit undetermined, candidate for CAD in the following systematic review.
CONCLUSIONS/SIGNIFICANCE
Our findings failed to demonstrate a correlation between (CAG)(n) polymorphism with CAD, however, we concluded that the rare 21-bp deletion might have a more compelling effect on CAD than the common (CAG)(n) polymorphism, and MEF2A genetic variant might be a rare but specific cause of CAD/MI.
Topics: Aged; Alleles; Base Pairing; Case-Control Studies; Coronary Artery Disease; Exons; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic Variation; Humans; MADS Domain Proteins; MEF2 Transcription Factors; Middle Aged; Myocardial Infarction; Myogenic Regulatory Factors; Polymorphism, Genetic; Risk Factors; Sequence Analysis, DNA; Sequence Deletion; Trinucleotide Repeat Expansion
PubMed: 22363637
DOI: 10.1371/journal.pone.0031406