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Journal of the Peripheral Nervous... Jun 2022Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were... (Review)
Review
BACKGROUND AND AIMS
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features.
METHODS
We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria.
RESULTS
A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
INTERPRETATION
This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.
Topics: Africa; Charcot-Marie-Tooth Disease; Genes, Recessive; Humans; Microfilament Proteins; Mutation; Phenotype; Proteins
PubMed: 35383421
DOI: 10.1111/jns.12489 -
JAMA Nov 2017High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain.
OBJECTIVE
To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome.
DATA SOURCES
Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017.
STUDY SELECTION
Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction.
DATA EXTRACTION AND SYNTHESIS
The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data.
RESULTS
Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death.
CONCLUSIONS AND RELEVANCE
Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.
Topics: Acute Coronary Syndrome; Adult; Biomarkers; Death; Humans; Male; Myocardial Infarction; Prognosis; Prospective Studies; Risk Assessment; Troponin I
PubMed: 29127948
DOI: 10.1001/jama.2017.17488 -
British Journal of Anaesthesia Nov 2016Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been shown to be an independent predictor of major adverse cardiac events and postoperative mortality; however, a majority of studies have focused on vascular surgery patients. The aim of this meta-analysis was to determine whether troponin elevation is a predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery.
METHODS
A systematic review and meta-analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials.
RESULTS
Eleven eligible clinical studies (n=2193) were identified. A postoperative troponin elevation was a predictor of 30 day mortality, odds ratio (OR) 3.52 [95% confidence interval (CI) 2.21-5.62; I=0%], and an independent predictor of 1 yr mortality, adjusted OR 2.53 (95% CI 1.20-5.36; I=26%). A postoperative troponin elevation was associated with major adverse cardiac events at 30 days, OR 5.92 (95% CI 1.67-20.96; I=86%), and 1 yr after surgery, adjusted OR 3.00 (95% CI 1.43-6.29; I=21%).
CONCLUSIONS
Postoperative myocardial injury is an independent predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. The meta-analysis provides evidence that supports troponin monitoring as a cardiovascular risk stratification tool.
Topics: Cardiovascular Diseases; Humans; Postoperative Complications; Troponin I
PubMed: 27799170
DOI: 10.1093/bja/aew321 -
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 -
International Journal of Molecular... Oct 2022Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform.... (Review)
Review
Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. We identified 25 "muscle fibre genes" (, , , , , , , , , , , , , , , , , , , , , , , and ) whose gain or loss-of-function significantly changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. A reanalysis of existing datasets revealed that the expression of and increases and decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population.
Topics: Adult; Mice; Animals; Humans; Muscle Fibers, Skeletal; Myosin Heavy Chains; Protein Isoforms; Electric Stimulation; Muscle, Skeletal; RNA-Binding Proteins; Forkhead Transcription Factors; Nuclear Receptor Co-Repressor 1
PubMed: 36361732
DOI: 10.3390/ijms232112933 -
Scandinavian Journal of Medicine &... Oct 2022The aim of this systematic review and meta-analysis was to identify the genetic variants of (inter)national competing long-distance runners and road cyclists compared... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review and meta-analysis was to identify the genetic variants of (inter)national competing long-distance runners and road cyclists compared with controls. The Medline and Embase databases were searched until 15 November 2021. Eligible articles included genetic epidemiological studies published in English. A homogenous group of endurance athletes competing at (inter)national level and sedentary controls were included. Pooled odds ratios based on the genotype frequency with corresponding 95% confidence intervals (95%CI) were calculated using random effects models. Heterogeneity was addressed by Q-statistics, and I . Sources of heterogeneity were examined by meta-regression and risk of bias was assessed with the Clark Baudouin scale. This systematic review comprised of 43 studies including a total of 3938 athletes and 10 752 controls in the pooled analysis. Of the 42 identified genetic variants, 13 were investigated in independent studies. Significant associations were found for five polymorphisms. Pooled odds ratio [95%CI] favoring athletes compared with controls was 1.42 [1.12-1.81] for ACE II (I/D), 1.66 [1.26-2.19] for ACTN3 TT (rs1815739), 1.75 [1.34-2.29] for PPARGC1A GG (rs8192678), 2.23 [1.42-3.51] for AMPD1 CC (rs17602729), and 2.85 [1.27-6.39] for HFE GG + CG (rs1799945). Risk of bias was low in 25 (58%) and unclear in 18 (42%) articles. Heterogeneity of the results was low (0%-20%) except for HFE (71%), GNB3 (80%), and NOS3 (76%). (Inter)national competing runners and cyclists have a higher probability to carry specific genetic variants compared with controls. This study confirms that (inter)national competing endurance athletes constitute a unique genetic make-up, which likely contributes to their performance level.
Topics: Humans; Actinin; Athletes; Genotype; Odds Ratio; Polymorphism, Genetic; Running; Bicycling
PubMed: 35839336
DOI: 10.1111/sms.14212 -
Sports Medicine (Auckland, N.Z.) May 2015'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic... (Review)
Review
BACKGROUND AND OBJECTIVE
'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW
All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using 'nitrogen dilution of oxygen' (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review.
SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES
Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English.
DATA COLLECTION AND ANALYSIS
Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies.
RESULTS
A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance (n = 5), running performance (n = 2), and maximum oxygen consumption ([Formula: see text]O2max) (n = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies.
CONCLUSION
The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies.
Topics: AMP Deaminase; Actinin; Altitude Sickness; Athletic Performance; Exercise; Genetic Variation; Genotype; Humans; INDEL Mutation; Oxygen Consumption; Peptidyl-Dipeptidase A
PubMed: 25682119
DOI: 10.1007/s40279-015-0309-8 -
International Journal of Sports Medicine Jul 2023The R577X polymorphism in the α-actinin-3 gene () is associated with muscle strength and power; there is an association between R577X polymorphism and range of motion... (Meta-Analysis)
Meta-Analysis
The R577X polymorphism in the α-actinin-3 gene () is associated with muscle strength and power; there is an association between R577X polymorphism and range of motion (ROM). We examined the effect of the R577X polymorphism on ROM through meta-analysis and systematic review. Relevant studies published before April 14, 2022 were identified from the PubMed database using the following keywords and Boolean operators: ("flexibility" or "Joint Range of Motion" or "Joint Flexibility" or "Range of motion") and ("ACTN3" or "alpha-actinin 3"). Studies that met the following criteria were included: (1) published in English, (2) included human subjects, (3) provided ROM measurements, and (4) analyzed the R577X genotype. A total of 2908 participants from seven studies were included in the meta-analysis. The additive genetic model was assessed using a meta-regression model, and dominant and recessive models were analyzed using a random effects model. The ROM in the XX+RX genotype was significantly higher than that in the RR genotype (recessive model: p<0.001), and it increased additively in the order XX>RX>RR (additive model: p=0.029). However, no significant association was observed in the dominant model. These findings further elucidate the association between flexibility and the R577X genotype.
Topics: Humans; Actinin; Genotype; Muscle Strength; Polymorphism, Genetic; Range of Motion, Articular
PubMed: 36787803
DOI: 10.1055/a-2035-8300 -
Journal of Sport and Health Science May 2023The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries... (Review)
Review
PURPOSE
The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs.
METHODS
A computerized literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus, from inception until November 2020. All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism.
RESULTS
Our search identified 492 records. After the screening of titles, abstracts, and full texts, 13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis. These studies were performed in 6 different countries (Spain, Japan, Brazil, China, the Republic of Korea, and Italy) and involved a total participant pool of 1093 participants. Of the studies, 2 studies involved only women, 5 studies involved only men, and 6 studies involved both men and women. All the studies included were classified as high-quality studies (≥6 points in the Physiotherapy Evidence Database (PEDro) scale score). Overall, evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations. Six studies observed a significant association between ACTN3 R577X polymorphism and exercise induced muscle damage: 2 with non-contact ankle injury, 3 with non-contact muscle injury, and 1 with overall non-contact injury.
CONCLUSION
The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries, such as muscle injury, ankle sprains, and higher levels of exercise-induced muscle damage.
Topics: Male; Humans; Female; Genotype; Polymorphism, Genetic; Exercise; Spain; Athletes; Actinin
PubMed: 34284153
DOI: 10.1016/j.jshs.2021.07.003 -
Indian Journal of Dental Research :... 2021The aim of this study is to review studies evaluating the role of genetics in skeletal class II malocclusion. (Review)
Review
AIM
The aim of this study is to review studies evaluating the role of genetics in skeletal class II malocclusion.
OBJECTIVE
To assess the scientific evidence associating the role of genes in skeletal class II malocclusion. Materials and Methods: A complete search across the electronic database through PubMed, Cochrane, LILACS, BMC and manual hand search of orthodontic journals were done till May 2019. The keywords for the search included: "Genetics", "class II malocclusion", "maxillary prognathism", "mandibular retrognathism".
DATA COLLECTION AND ANALYSIS
Studies were selected based on PRISMA guidelines.
RESULTS
Articles were selected based on the inclusion and exclusion criteria. A total of 11 cross-sectional studies satisfied the inclusion criteria and were analyzed for the role of genes in skeletal class II malocclusion. Almost all the studies except for one revealed a positive correlation of genes with skeletal class II malocclusion.
CONCLUSIONS
Out of the 11 studies included, a positive correlation of the genes with the skeletal II malocclusion was found in 10 studies. Genes FGFR2, MSX1, MATN1, MYOH1, ACTN3, GHR, KAT6B, HDAC4, AJUBA were found to be positively linked to skeletal class II malocclusion.
Topics: Actinin; Cephalometry; Cross-Sectional Studies; Histone Acetyltransferases; Humans; LIM Domain Proteins; Malocclusion; Malocclusion, Angle Class II; Malocclusion, Angle Class III
PubMed: 35229783
DOI: 10.4103/ijdr.IJDR_59_20