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Frontiers in Cardiovascular Medicine 2023Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are...
INTRODUCTION
Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.
METHODS
A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between 4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; = .003]. Additionally, there was a significant association between patients possessing at least one 4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; = .03). Lastly, there was no association between 4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; = .30).
CONCLUSION
APOE 4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.
PubMed: 38034385
DOI: 10.3389/fcvm.2023.1155916 -
Genetics in Medicine : Official Journal... Oct 2010Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related phenotype of ischemic stroke are inconclusive. We performed a meta-analysis of published studies investigating the association between ischemic stroke and two nonsynonymous PON1 polymorphisms, rs662 (p.Q192R) and rs854560 (p.L55M) in humans.
METHODS
We searched multiple electronic databases through June 30, 2009 for eligible studies. In main analyses, we calculated allele-based odds ratios with random effects models. In secondary analyses, we examined dominant and recessive genetic models as well, and performed subgroup and sensitivity analyses.
RESULTS
Regarding rs662, we identified 22 eligible studies (total of 7384 cases/11,074 controls), yielding a summary odds ratio of 1.10 per G allele (95% confidence interval, 1.04-1.17) with no evidence of between-study heterogeneity. For rs854560, 16 eligible studies (total of 5518 cases/8951 controls) yielded a summary odds ratio of 0.97 per T allele (95% confidence interval, 0.90-1.04), again with no evidence of between-study heterogeneity. For both polymorphisms, analyses with dominant and recessive genetic models yielded the same inferences as allele-based comparisons. Subgroup and sensitivity analyses showed similar results.
CONCLUSION
In agreement with observations in coronary artery disease, PON1 rs662 appears to be associated with a small increase in the risk of ischemic stroke.
Topics: Alleles; Aryldialkylphosphatase; Brain Ischemia; Confidence Intervals; Coronary Disease; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Phenotype; Polymorphism, Genetic; Risk Factors; Stroke
PubMed: 20856122
DOI: 10.1097/GIM.0b013e3181ee81c6 -
Pharmaceutics Feb 2022Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted... (Review)
Review
Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted with small sample sizes, making it challenging to apply the findings clinically. Therefore, the purpose of this study is to perform a meta-analysis of the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. We searched three electronic databases, EMBASE, PubMed, and Web of Science, using search terms related to ABCG2 gene polymorphisms and rosuvastatin. In addition, we reviewed studies published before 12 August 2021, to examine the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. To examine the magnitude of the association, the log geometric mean difference (lnGM) and 95% confidence intervals (CIs) were calculated and interpreted as the antilogarithm of a natural logarithm (elnGM). The meta-analysis was performed using Review Manager (version 5.4) and R Studio (version 4.0.2). Subgroup analysis was performed according to race and the types of mean values. Among the 318 identified studies, a total of 8 studies involving 423 patients is included in this meta-analysis. The A allele carriers of ABCG2 421C>A showed 1.5 times higher in both AUC0-∞ (lnGM = 0.43; 95% CI = 0.35−0.50; p < 0.00001) and Cmax (lnGM = 0.42; 95% CI = 0.33−0.51; p < 0.00001) than non-carriers, while there was no significant difference in Tmax and half-life. There was no significance in the pharmacokinetic parameters of the subgroups using either ethnicity or mean values. This meta-analysis demonstrates that subjects carrying the A allele of ABCG2 421C>A show significantly increased AUC0-∞ and Cmax values compared to subjects with the CC genotype. Therefore, information about ABCG2 genotypes might be useful for individualized rosuvastatin therapy.
PubMed: 35335877
DOI: 10.3390/pharmaceutics14030501 -
Journal of Lipid Research Oct 2010Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a... (Meta-Analysis)
Meta-Analysis Review
Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 ± 10.5 years; BMI, 23.9 ± 3.5 kg/m(2)). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant [n = 614; -0.11 mmol/l (95% CI, range: -0.20 to -0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Adult; Cholesterol; Genotype; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Polymorphism, Genetic
PubMed: 20581104
DOI: 10.1194/jlr.M008128 -
Frontiers in Psychiatry 2022We aimed to examine the association of polymorphisms with the risk of suicide behavior (SB).
OBJECTIVES
We aimed to examine the association of polymorphisms with the risk of suicide behavior (SB).
DESIGN
Systematic review and meta-analysis.
METHOD
All relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association between gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis.
RESULTS
The meta-analysis for A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01-1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05-1.21), homozygous (OR = 1.22, 95%CI 1.06-1.40), heterozygous (OR = 1.21, 95%CI 1.08-1.37) and dominant (OR = 1.21, 95%CI 1.09-1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73-0.97) and dominant (OR = 0.79, 95%CI 0.68-0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12-1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB.
CONCLUSION
This meta-analysis suggests that the A218C polymorphism of gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.
PubMed: 35928776
DOI: 10.3389/fpsyt.2022.932135 -
Journal of Cardiovascular Development... Feb 2023A cluster of three genes , , and has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated... (Review)
Review
A cluster of three genes , , and has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13-1.26, dominant OR 1.22, 95% CI 1.06-1.39, recessive OR 1.23, 95% CI 1.15-1.32), rs646776 (allelic OR 1.46, 95% CI 1.17-1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease.
PubMed: 36975855
DOI: 10.3390/jcdd10030091 -
PLoS Medicine Jun 2023Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs).
METHODS AND FINDINGS
We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders.
CONCLUSIONS
We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.
Topics: Adult; Humans; Developing Countries; Inpatients; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Sepsis; Bacteria; Anti-Bacterial Agents
PubMed: 37347726
DOI: 10.1371/journal.pmed.1004199 -
Scientific Reports Jul 2022Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators... (Meta-Analysis)
Meta-Analysis
Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators such as IFN-γ and nitric oxide. Studies have shown that specific polymorphisms are associated with the regulatory role of IL-10 and the development of more relevant clinical forms of leishamaniasis. We performed a systematic review and meta-analysis to determine whether single nucleotide polymorphisms (SNPs) of IL-10 influence the progression of leishmaniasis. The selected articles were read in full and only those consistent with the eligibility criteria were included in our study. Seven studies were eligible according to the inclusion criteria and were included in the present systematic review, but only five were subjected to statistical analysis. The pooled odds ratios showed no significant association between the rs1800871 SNP and the progression of leishmaniasis in all genotype models, including the dominant, recessive, homozygote, heterozygote, and allelic models. Regarding the association between rs1800896 SNP and the progression of leishmaniasis, the pooled odds ratios showed no association under all genotype models. Hence, IL-10 SNPs did not show significant association and were not considered a risk factor for the progression of leishmaniasis.
Topics: Alleles; Genetic Predisposition to Disease; Humans; Interleukin-10; Leishmaniasis; Polymorphism, Single Nucleotide
PubMed: 35778471
DOI: 10.1038/s41598-022-15377-2 -
Pain Physician 2015Adolescent idiopathic scoliosis (AIS) is a tridimensional structural deformity of the spine that may deteriorate progressively, leading to significant functional... (Meta-Analysis)
Meta-Analysis Review
The Association of rs4753426 Polymorphism in the Melatonin Receptor 1B (MTNR1B) Gene and Susceptibility to Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.
BACKGROUND
Adolescent idiopathic scoliosis (AIS) is a tridimensional structural deformity of the spine that may deteriorate progressively, leading to significant functional limitations and pain problems. Several previous studies have implicated the rs4753426 single nucleotide polymorphism in the melatonin receptor 1B (MTNR1B) gene in the etiology of AIS. However the sample sizes were limited and the findings of those studies were inconsistent. An overall assessment of the evidence supporting this association has not been previously conducted.
OBJECTIVES
To provide a comprehensive assessment and synthesis of the currently available evidence on the association between rs4753426 and AIS.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
University hospital, China.
METHODS
This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus databases, and WANFANG databases were systematically searched through December 2014 to identify relevant studies following a sensitive strategy. Statistical analysis was performed using the Review Manager 5.2 software. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using the fixed-effect inverse variance model for allelic (C vs. T) and genotypic comparisons.
RESULTS
Four papers including 5 studies which involved 2,552 AIS cases and 2,738 controls were identified for this meta-analysis. The results showed that C allele of the rs4753426 was significantly associated with AIS (OR = 1.12, 95% CI: 1.03-1.21, P = 0.01). CT and CC genotypes were 26% (OR = 1.26, 95% CI: 1.04-1.53, P = 0.01) and 28% (OR = 1.28, 95% CI: 1.05-1.56, P = 0.01), respectively, more likely to have AIS compared with CC genotype. As for the dominant model (CC+TT vs. TT), summary ORs showed statistically significant association with AIS (OR = 1.28, 95% CI: 1.06-1.53, P = 0.009). Compared with the CT+TT genotype, the summary ORs of the CC genotype showed marginally statistically significant association with AIS (OR = 1.11, 95 % CI: 0.99-1.24, P = 0.07). The subgroup meta-analysis results showed the C allele and each genotype were significantly associated with AIS in the Asian group but not in the Caucasian group.
LIMITATIONS
Paucity of available literature.
CONCLUSIONS
To our knowledge, there has been no meta-analysis to analyze the association between rs4753426 polymorphism in the MTNR1B gene and AIS. This systematic review was a comprehensive analysis of the currently available evidence, and found an overall significant association of rs4753426 polymorphism with the risk of AIS, especially in the Asian population. Further investigation of this association is necessary in other populations.
Topics: Adolescent; Asian People; Gene Frequency; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptor, Melatonin, MT2; Scoliosis
PubMed: 26431121
DOI: No ID Found -
PloS One 2014Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln) and treatment outcomes of patients with advanced gastric cancer.
METHODOLOGY/PRINCIPAL FINDINGS
We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR) for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated by pooled Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs). We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet.
CONCLUSIONS/SIGNIFICANCE
There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification.
Topics: Adult; Aged; Alleles; Antineoplastic Agents; Cisplatin; DNA-Binding Proteins; Databases, Bibliographic; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Stomach Neoplasms; Survival Analysis; Treatment Outcome; X-ray Repair Cross Complementing Protein 1
PubMed: 24465544
DOI: 10.1371/journal.pone.0085357