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The British Journal of Dermatology Mar 2013Despite acne being an almost universal condition in younger people, relatively little is known about its epidemiology. We sought to review what is known about the... (Review)
Review
Despite acne being an almost universal condition in younger people, relatively little is known about its epidemiology. We sought to review what is known about the distribution and causes of acne by conducting a systematic review of relevant epidemiological studies. We searched Medline and Embase to the end of November 2011. The role of Propionibacterium acnes in pathogenesis is unclear: antibiotics have a direct antimicrobial as well as an anti-inflammatory effect. Moderate-to-severe acne affects around 20% of young people and severity correlates with pubertal maturity. Acne may be presenting at a younger age because of earlier puberty. It is unclear if ethnicity is truly associated with acne. Black individuals are more prone to postinflammatory hyperpigmentation and specific subtypes such as 'pomade acne'. Acne persists into the 20s and 30s in around 64% and 43% of individuals, respectively. The heritability of acne is almost 80% in first-degree relatives. Acne occurs earlier and is more severe in those with a positive family history. Suicidal ideation is more common in those with severe compared with mild acne. In the U.S.A., the cost of acne is over 3 billion dollars per year in terms of treatment and loss of productivity. A systematic review in 2005 found no clear evidence of dietary components increasing acne risk. One small randomized controlled trial showed that low glycaemic index (GI) diets can lower acne severity. A possible association between dairy food intake and acne requires closer scrutiny. Natural sunlight or poor hygiene are not associated. The association between smoking and acne is probably due to confounding. Validated core outcomes in future studies will help in combining future evidence.
Topics: Acne Vulgaris; Adolescent; Adult; Cacao; Child; Chronic Disease; Dairy Products; Diet; Ethnicity; Female; Glycemic Index; Humans; Hygiene; Male; Middle Aged; Obesity; Pedigree; Prevalence; Propionibacterium acnes; Risk Factors; Smoking; Socioeconomic Factors; Stress, Psychological; Sunlight; Young Adult
PubMed: 23210645
DOI: 10.1111/bjd.12149 -
European Journal of Medical Genetics Oct 2021Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset...
Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset diffuse gastric cancer (DGC) and/or invasive lobular breast cancer (LBC) are the main phenotypes in CDH1-associated HDGC. CTNNA1, encoding for α-E-catenin, and E-cadherin-partner in the adherens junction complex, has been recently classified as a HDGC predisposing gene. Nevertheless, little is known about CTNNA1 tumor spectrum in variant carriers and variant-type associated causality. Herein, we systematically reviewed the literature searching for CTNNA1 germline variants carriers, further categorized them according to HDGC clinical criteria (HDGC vs non-HDGC), collected phenotypes, classified variants molecularly and according to CDH1 ACMG/AMP guidelines and performed genotype-phenotype analysis. We found 41 families carrying CTNNA1 germline variants encompassing in total 105 probands and relatives. All probands from 13 HDGC families presented DGC and their average age of onset was 40 ± 17 years; 10/13 (77%) HDGC families carried a pathogenic (P) variant. Most probands from 28 non-HDGC families developed unspecified-BC, as well as most of their relatives; 4/28 (14%) carried a P variant, 16/28 (57%) carried a likely pathogenic (LP) variant, 7/28 (25%) carried variants of unknown significance (VUS) and 1/28 (4%) carried a likely benign variant. Regardless of clinical criteria, 97% (32/33) of probands and relatives from P variant-carrier families had DGC/unspecified-GC. In LP variant-carrier families, 82% (28/34) of probands and relatives had unspecified-BC. Only 2/105 individuals had LBC. A cluster of frameshift and nonsense variants was found in CTNNA1 last exon of non-HDGC families and classified as VUS. In conclusion, current available data confirms an association of CTNNA1 P variants with early-onset DGC, but not with LBC. We demonstrate that in ascertained cohorts, CTNNA1 P variants explain <2% of HDGC families and support the use of ACMG/AMP CDH1 specific variant curation guidelines, while no specific guidelines are developed for CTNNA1 variant classification. Moreover, we demonstrated that truncating variants at the CTNNA1 NMD-incompetent last exon have limited deleteriousness, and that CTNNA1 LP variants have lower actionability than CDH1 LP variants. Current knowledge supports considering only CTNNA1 P variants as clinically actionable in HDGC carrying families.
Topics: Antigens, CD; Cadherins; Gene Frequency; Genetic Predisposition to Disease; Germ-Line Mutation; Heterozygote; Humans; Pedigree; Phenotype; Stomach Neoplasms; alpha Catenin
PubMed: 34425242
DOI: 10.1016/j.ejmg.2021.104316 -
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Journal of Human Genetics May 2015Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD... (Meta-Analysis)
Meta-Analysis Review
Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/.
Topics: Age of Onset; Alzheimer Disease; Chromosomes, Human, Pair 17; Frontotemporal Dementia; Genetic Predisposition to Disease; Humans; Mutation
PubMed: 25694106
DOI: 10.1038/jhg.2015.15 -
PloS One 2014The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies.
METHODS AND FINDINGS
Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled odds ratio (OR) of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45-0.84), and the pooled OR for allergies was 1.01 (95% CI 0.62-1.69). The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25-0.58). Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies.
CONCLUSIONS
Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence.
Topics: Adult; Asthma; Child; Emigration and Immigration; Environment; Humans; Pedigree; Prevalence
PubMed: 25141011
DOI: 10.1371/journal.pone.0105347 -
JAMA Ophthalmology Sep 2013Understanding the development of common strabismus is important in locating "at-risk" populations and implementing optimal treatment. This systematic review will bring... (Review)
Review
IMPORTANCE
Understanding the development of common strabismus is important in locating "at-risk" populations and implementing optimal treatment. This systematic review will bring together reported genetic and environmental risk factors for common strabismus to reveal relationships between risk factors and guide future research.
OBJECTIVE
To identify known environmental and genetic risk factors for comitant strabismus reported in the literature.
DATA SOURCES
A systematic literature search was performed in Medline, Embase, BioSciences Information Service Previews, Web of Science, and the OMIM database during a 2-week period in July 2011 (including all available years) using the following key words: gene, genetic environmental factor, inheritance, risk factor, esotropia, exotropia, strabismus, squint, convergent strabismus, and divergent strabismus.
STUDY SELECTION
No language restrictions were placed on the search. Exclusion criteria consisted of associated syndromes, strabismus not the primary outcome, poor study design or quality, and logarithm of the odds score less than 3.
DATA EXTRACTION AND SYNTHESIS
A study quality and extraction tool was used. Analysis was performed descriptively because of the variant characteristics of the study designs.
MAIN OUTCOMES AND MEASURES
Risk factor, twin, pedigree, and genetic studies.
RESULTS
Forty-one articles fulfilled the inclusion criteria set out by the study, which highlighted 4 subcategories: risk factor, twin, pedigree, and genetic studies. Significant risk factors for strabismus reported by the studies included low birth weight, cicatricial retinopathy of prematurity, prematurity, smoking throughout pregnancy, anisometropia, hyperopia, and inheritance. Inheritance was further supported by twin and pedigree studies, which revealed the complexity of the inheritance pattern. At present the STBMS1 locus is the only gene location that has been supported; however, others have been reported.
CONCLUSIONS AND RELEVANCE
Certain subgroups within the population are at higher risk of developing comitant strabismus and should be identified and monitored to allow for earlier detection. It is evident that a strong hereditary link is present particularly in intermittent and accommodative forms; however, further research is required to identify possible links between subtypes of strabismus. Further genetic research could also help to locate additional causative genes to aid the understanding of strabismus development.
Topics: Birth Weight; Child, Preschool; Female; Gestational Age; Humans; Infant; Infant, Newborn; Pedigree; Pregnancy; Pregnancy Complications; Retinopathy of Prematurity; Risk Factors; Strabismus; Twin Studies as Topic
PubMed: 23846622
DOI: 10.1001/jamaophthalmol.2013.4001 -
BMJ Clinical Evidence Oct 2007Nocturnal enuresis affects 15-20% of 5-year-old children, 5% of 10 year-old-children and 1-2% of people aged 15 years and over. Without treatment, 15% of affected... (Review)
Review
INTRODUCTION
Nocturnal enuresis affects 15-20% of 5-year-old children, 5% of 10 year-old-children and 1-2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year. Nocturnal enuresis is not diagnosed in children younger than 5 years, and treatment may be inappropriate for children younger than 7 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for relief of symptoms? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, anticholinergics (oxybutynin, tolterodine, hyoscyamine), desmopression, dry bed training, enuresis alarm, hypnotherapy, standard home alarm clock, tricyclics (imipramine, desipramine).
Topics: Acupuncture Therapy; Age Factors; Antidepressive Agents, Tricyclic; Desipramine; Genetic Linkage; Humans; Imipramine; Nocturnal Enuresis; Pedigree; Prospective Studies; Time Factors
PubMed: 19450363
DOI: No ID Found -
BioMed Research International 2023LHON is a progressive disease with early disease onset and male predominance, usually causing devastating visual loss to patients. These systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
LHON is a progressive disease with early disease onset and male predominance, usually causing devastating visual loss to patients. These systematic review and meta-analysis are aimed at summarizing epidemiology, disease onset and progression, visual recovery, risk factors, and treatment options of Leber's hereditary optic neuropathy (LHON) with mitochondrial DNA mutation G11778A from current evidence.
METHODS
The PubMed database was examined from its inception date to November 2021. Data from included studies were pooled with either a fixed-effects model or a random-effects model, depending on the results of heterogeneity tests. Sensitivity analysis was conducted to test the robustness of results.
RESULTS
A total of 41 articles were included in the systematic review for qualitative analysis, and 34 articles were included for quantitative meta-analysis. The pooled estimate of proportion of G11778A mutation among the three primary mutations of mitochondrial DNA (G11778A, G3460A, and T14484C) for LHON was 73% (95% CI: 67% and 79%), and the LHON patients with G11778A mutation included the pooled male ratio estimate of 77% (76% and 79%), the pooled age estimate of 35.3 years (33.2 years and 37.3 years), the pooled onset age estimate of 22.1 years (19.7 years and 24.6 years), the pooled visual acuity estimate of 1.4 LogMAR (1.2 LogMAR and 1.6 LogMAR), and the pooled estimate of spontaneous visual recovery rate (in either 1 eye) of 20% (15% and 27%).
CONCLUSIONS
The G11778A mutation is a prevalent mitochondrial DNA mutation accounting for over half of LHON cases with three primary mutations. Spontaneous visual recovery is rare, and no effective treatment is currently available.
Topics: Adult; Female; Humans; Male; Young Adult; DNA, Mitochondrial; Mitochondria; Mutation; Optic Atrophy, Hereditary, Leber; Pedigree
PubMed: 36743514
DOI: 10.1155/2023/1107866 -
Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis.European Journal of Vascular and... Jan 2016Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE/BACKGROUND
Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.
METHODS
Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.
RESULTS
Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.
CONCLUSION
Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.
Topics: Aortic Aneurysm, Abdominal; Genetic Predisposition to Disease; Heredity; Humans; Odds Ratio; Pedigree; Phenotype; Polymorphism, Genetic; Risk Assessment; Risk Factors
PubMed: 26460285
DOI: 10.1016/j.ejvs.2015.09.006 -
Fertility and Sterility Feb 2018To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis Review
Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis.
OBJECTIVE
To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS).
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Mothers, fathers, sisters, and brothers of women with and without PCOS.
INTERVENTION(S)
An electronic-based search with the use of PubMed from 1960 to June 2015 and cross-checked references of relevant articles.
MAIN OUTCOME MEASURE(S)
Metabolic syndrome, hypertension and dyslipidemia, and surrogate markers, including systolic blood pressure (BP), diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides.
RESULT(S)
Fourteen of 3,346 studies were included in the meta-analysis. Prevalence of the following was significantly increased in relatives of women with PCOS: metabolic syndrome (risk ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12, 1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58, 2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54, 5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low-density lipoprotein cholesterol (sisters), and triglycerides (mothers and sisters) were significantly higher in first-degree relatives of PCOS probands than in controls.
CONCLUSION(S)
Our results show evidence of clustering for metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters, and brothers of women with PCOS.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO 2016 CRD42016048557.
Topics: Adolescent; Adult; Chi-Square Distribution; Cluster Analysis; Evidence-Based Medicine; Family; Female; Genetic Predisposition to Disease; Heredity; Humans; Hyperlipidemias; Hypertension; Male; Metabolic Syndrome; Middle Aged; Odds Ratio; Pedigree; Phenotype; Polycystic Ovary Syndrome; Prevalence; Risk Assessment; Risk Factors; Young Adult
PubMed: 29331234
DOI: 10.1016/j.fertnstert.2017.10.018