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Nutrition, Metabolism, and... Jun 2024The impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
The impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established correlation with diminished blood cholesterol levels. This meta-analysis aimed at exploring the effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and CVD.
METHODS AND RESULTS
PubMed, Embase, and the Cochrane Library were searched for cohort and case-control studies published until October 1, 2023. The studies should report the association of the PCSK9 R46L genetic variant with one of the following: fasting plasma insulin, blood glucose levels, diabetes mellitus, and CVD risk. A dominant model of the PCSK9 R46L genetic variant was employed to statistical analysis. The meta-analyses were performed for continuous variables with standard mean difference (SMD), categorical variables with odds ratio (OR) using a random-effects model. A total of 17 articles with 20 studies engaging 1,186,861 population were identified and mobilized for these analyses. The overall results indicated that, compared with non-carriers of the PCSK9 R46L genetic variant, carriers of the PCSK9 R46L genetic variant did not increase or decrease the levels of fasting plasma insulin (3 studies with 7277 population; SMD, 0.08; 95% CI, -0.04 to 0.19; P = 0.270), and the levels of fasting plasma glucose (7 studies with 9331 population; SMD, 0.03; 95% CI, -0.08 to 0.13; P = 0.610). However, carriers of the PCSK9 R46L genetic variant indeed had 17% reduction in the risk of CVD (11 studies with 558,263 population; OR, 0.83; 95% CI, 0.71 to 0.98; P = 0.030), and 9% increase in the risk of diabetes mellitus (10 studies with 744,466 population; OR, 1.09; 95% CI, 1.04 to 1.14; P < 0.01). Meta-regression analyses indicated that the increased risk of diabetes mellitus and the reduced risk of CVD were positively correlated with reduction in LDL-C (P = 0.004 and 0.033, respectively).
CONCLUSIONS
PCSK9 R46L genetic variant exhibited an elevated susceptibility to diabetes mellitus alongside a reduced vulnerability to CVD.
Topics: Humans; Proprotein Convertase 9; Cardiovascular Diseases; Blood Glucose; Genetic Predisposition to Disease; Insulin; Risk Assessment; Biomarkers; Diabetes Mellitus; Female; Male; Middle Aged; Phenotype; Adult; Aged; Loss of Function Mutation; Risk Factors; Young Adult; Heart Disease Risk Factors
PubMed: 38734541
DOI: 10.1016/j.numecd.2024.04.007 -
International Journal of Molecular... May 2024Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for... (Meta-Analysis)
Meta-Analysis Review
Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case-control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case-control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02-1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54-1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70-1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84-1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible.
Topics: Humans; Anterior Cruciate Ligament Injuries; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Interleukin-6; Interleukin-1beta; Receptors, Interleukin-6; Interleukins; Risk Factors; Case-Control Studies
PubMed: 38732195
DOI: 10.3390/ijms25094976 -
International Journal of Molecular... Apr 2024Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of... (Review)
Review
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
Topics: Humans; Autism Spectrum Disorder; Neuroimaging; Brain; Electroencephalography; Genetic Predisposition to Disease
PubMed: 38732157
DOI: 10.3390/ijms25094938 -
Gastroenterology Research Apr 2024Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and...
BACKGROUND
Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model.
RESULTS
Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I = 0%).
CONCLUSIONS
In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.
PubMed: 38716286
DOI: 10.14740/gr1672 -
Heliyon Apr 2024Magnetic resonance imaging (MRI) techniques, such as quantitative susceptibility mapping (QSM) and susceptibility-weighted imaging (SWI), can detect iron deposition in...
Parkinson's disease and Parkinsonism syndromes: Evaluating iron deposition in the putamen using magnetic susceptibility MRI techniques - A systematic review and literature analysis.
Magnetic resonance imaging (MRI) techniques, such as quantitative susceptibility mapping (QSM) and susceptibility-weighted imaging (SWI), can detect iron deposition in the brain. Iron accumulation in the putamen (PUT) can contribute to the pathogenesis of Parkinson's disease (PD) and atypical Parkinsonian disorders. This systematic review aimed to synthesize evidence on iron deposition in the PUT assessed by MRI susceptibility techniques in PD and Parkinsonism syndromes. The PubMed and Scopus databases were searched for relevant studies. Thirty-four studies from January 2007 to October 2023 that used QSM, SWI, or other MRI susceptibility methods to measure putaminal iron in PD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HCs) were included. Most studies have found increased putaminal iron levels in PD patients versus HCs based on higher quantitative susceptibility. Putaminal iron accumulation correlates with worse motor scores and cognitive decline in patients with PD. Evidence regarding differences in susceptibility between PD and atypical Parkinsonism is emerging, with several studies showing greater putaminal iron deposition in PSP and MSA than in PD patients. Alterations in putaminal iron levels help to distinguish these disorders from PD. Increased putaminal iron levels appear to be associated with increased disease severity and progression. Thus, magnetic susceptibility MRI techniques can detect abnormal iron accumulation in the PUT of patients with Parkinsonism. Moreover, quantifying putaminal susceptibility may serve as an MRI biomarker to monitor motor and cognitive changes in PD and aid in the differential diagnosis of Parkinsonian disorders.
PubMed: 38689949
DOI: 10.1016/j.heliyon.2024.e27950 -
Frontiers in Aging Neuroscience 2024Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by...
Associations of vitamin D receptor polymorphisms with risk of Alzheimer's disease, Parkinson's disease, and mild cognitive impairment: a systematic review and meta-analysis.
Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (I, I, I, and I) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the I polymorphism decreased the overall AD risk, and the I increased the overall PD susceptibility. In addition, the I and I polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the I and I genotypes reduced the AD predisposition among Caucasians, while the I polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the I variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility.
PubMed: 38681668
DOI: 10.3389/fnagi.2024.1377058 -
Genes Apr 2024Normal tension glaucoma (NTG) is becoming a more and more serious problem, especially in Asia. But the pathological mechanisms are still not illustrated clearly. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Normal tension glaucoma (NTG) is becoming a more and more serious problem, especially in Asia. But the pathological mechanisms are still not illustrated clearly. We carried out this research to uncover the gene polymorphisms with NTG.
METHODS
We searched in Web of Science, Embase, Pubmed and Cochrane databases for qualified case-control studies investigating the association between single nucleotide polymorphisms (SNPs) and NTG risk. Odds ratios (ORs) and 95% confidence intervals (CIs) for each SNP were estimated by fixed- or random-effect models. Sensitivity analysis was also performed to strengthen the reliability of the results.
RESULTS
Fifty-six studies involving 33 candidate SNPs in 14 genetic loci were verified to be eligible for our meta-analysis. Significant associations were found between 16 SNPs (rs166850 of ; rs10451941 of ; rs735860 of ; rs678350 of ; c.603T>A/Met98Lys of ; c.412G>A/Thr34Thr of ; rs10759930 of ; rs1927914 of ; rs1927911 of ; c.*70C>G of ; rs1042522/-Arg72Pro of ; rs10483727 of ; rs33912345 of ; rs2033008 of ; rs3213787 of and c.231G>A of ) with increased or decreased risk of NTG.
CONCLUSIONS
In this study, we confirmed 16 genetic polymorphisms in 10 genes (, , , , , , , , and ) were associated with NTG.
Topics: Humans; Case-Control Studies; Genetic Predisposition to Disease; Low Tension Glaucoma; Polymorphism, Single Nucleotide
PubMed: 38674425
DOI: 10.3390/genes15040491 -
Medicine Apr 2024Parkinson disease (PD) is a common neurodegenerative disorder, but its pathogenesis is still not entirely understood. While some trace elements, such as selenium, iron,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson disease (PD) is a common neurodegenerative disorder, but its pathogenesis is still not entirely understood. While some trace elements, such as selenium, iron, and copper, are considered pivotal in PD onset due to their role in oxidative stress, the association between selenium concentrations and PD susceptibility remains ambiguous.
METHODS
A systematic review and meta-analysis was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and framed by the Patient, Intervention, Comparison, Outcome paradigm. Data were sourced from 4 prominent electronic databases: PubMed, Embase, Web of Science, and Cochrane Library. Eligible studies must have had a PD case group and a control group, both of which presented data on selenium concentrations. The quality of the studies was assessed using the Newcastle-Ottawa Scale.
RESULTS
Of 1541 initially identified articles, 12 studies comprising a total of 597 PD cases and 733 controls were selected for the meta-analysis. Pronounced heterogeneity was observed among these studies. When assessing blood selenium levels, no significant difference was found between patients with PD and the controls. However, when examining the cerebrospinal fluid, selenium levels in PD patients were significantly elevated compared to controls (standard mean difference = 1.21, 95% CI 0.04-2.39, P < .05). Subgroup analyses, sensitivity analyses, and evaluation of publication bias were performed to ensure data robustness.
CONCLUSIONS
Elevated selenium levels in cerebrospinal fluid may be associated with a higher risk of Parkinson. Further prospective research is required to solidify this potential link and to offer avenues for novel therapeutic interventions or preventive measures.
Topics: Humans; Selenium; Parkinson Disease
PubMed: 38669409
DOI: 10.1097/MD.0000000000037919 -
Strahlentherapie Und Onkologie : Organ... Jul 2024To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and... (Meta-Analysis)
Meta-Analysis
PURPOSE
To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD.
METHODS
This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE.
RESULTS
Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFβ1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with a similar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed a statistically significant association with very low certainty of evidence.
CONCLUSION
The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be a promising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have a customized treatment. This current review provides new research directions.
Topics: Humans; Genetic Markers; Genetic Predisposition to Disease; Head and Neck Neoplasms; Polymorphism, Single Nucleotide; Radiodermatitis; Risk Factors
PubMed: 38668865
DOI: 10.1007/s00066-024-02237-3 -
Eating and Weight Disorders : EWD Apr 2024Several studies have investigated the association between anorexia nervosa and polymorphisms of genes regulating serotonin neurotransmission, with a focus on the rs6311... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Several studies have investigated the association between anorexia nervosa and polymorphisms of genes regulating serotonin neurotransmission, with a focus on the rs6311 polymorphism of 5-HTR2A. However, inconsistent results of these studies and conflicting conclusions of existing meta-analyses complicate the understanding of a possible association. We have updated these results and evaluated the involvement of other serotonin receptor gene polymorphisms in anorexia nervosa.
METHODS
Adhering to PRISMA guidelines, we have searched studies on anorexia nervosa and serotonin-regulating genes published from 1997 to 2022, selected those concerning receptor genes and meta-analyzed the results from twenty candidate gene studies on the 5-HTR2A rs6311 polymorphism and the 5-HTR2C rs6318 polymorphism.
RESULTS
Present analyses reveal an association for the 5-HTR2A rs6311 polymorphism, with G and A alleles, across eighteen studies (2049 patients, 2877 controls; A vs. G allele, Odds Ratio = 1.24; 95% Confidence Interval = 1.06-1.47; p = 0.009). However, after geographic subgrouping, an association emerged only in a Southern European area, involving five studies (722 patients, 773 controls; A vs. G allele, Odds Ratio = 1.82; 95% Confidence Interval = 1.41-2.37; p < 0.00001). No association was observed for the 5-HTR2C rs6318 polymorphism across three studies.
CONCLUSIONS
To date, the involvement in the pathophysiology of anorexia nervosa of the 5-HTR2A rs6311 polymorphism appears limited to a specific genetic and/or environmental context, while that of the 5-HTR2C rs6318 polymorphism seems excluded. Genome-wide association studies and epigenetic studies will likely offer deeper insights of genetic and environmental factors possibly contributing to the disorder.
LEVEL OF EVIDENCE
III Evidence obtained from well-designed cohort or case-control analytic studies. Clinical trial registration PROSPERO registration number: CRD42021246122.
Topics: Humans; Anorexia Nervosa; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C
PubMed: 38668826
DOI: 10.1007/s40519-024-01659-3