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Malaria Journal Apr 2024In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive... (Meta-Analysis)
Meta-Analysis Review
Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA.
METHODS
The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17.
RESULTS
The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%).
CONCLUSION
The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.
Topics: Humans; Merozoite Surface Protein 1; Plasmodium falciparum; Antigens, Protozoan; Protozoan Proteins; Genetic Markers; Genetic Variation; Malaria, Falciparum; Genotype; Alleles; Microsatellite Repeats; South Africa
PubMed: 38589874
DOI: 10.1186/s12936-024-04925-y -
BMC Cardiovascular Disorders Apr 2024The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency.
METHODS
PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023.
RESULTS
Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals.
CONCLUSIONS
The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Genetic Predisposition to Disease; Cholesterol, LDL; Dyslipidemias; ATP Binding Cassette Transporter, Subfamily G, Member 2; Neoplasm Proteins
PubMed: 38589776
DOI: 10.1186/s12872-024-03821-2 -
JAMA Dermatology May 2024Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear.
OBJECTIVE
To investigate the association between HLA genotypes and SMX/CTX-induced SCARs.
DATA SOURCES
A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023.
STUDY SELECTION
Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed.
DATA EXTRACTION AND SYNTHESIS
Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis.
MAIN OUTCOMES AND MEASURES
The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles.
RESULTS
Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82).
CONCLUSIONS AND RELEVANCE
The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HLA Antigens; Drug Eruptions; Sulfamethoxazole; Genotype; Severity of Illness Index; Anti-Bacterial Agents; Case-Control Studies
PubMed: 38568509
DOI: 10.1001/jamadermatol.2024.0210 -
JAMA Ophthalmology May 2024Effects of genetic variants on primary angle-closure disease remained uncertain. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Effects of genetic variants on primary angle-closure disease remained uncertain.
OBJECTIVE
To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression.
DATA SOURCES
Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen.
STUDY SELECTION
Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics.
MAIN OUTCOMES AND MEASURES
SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized.
RESULTS
Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified.
CONCLUSIONS AND RELEVANCE
This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.
Topics: Glaucoma, Angle-Closure; Humans; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Genetic Predisposition to Disease; Intraocular Pressure
PubMed: 38546604
DOI: 10.1001/jamaophthalmol.2024.0363 -
Frontiers in Genetics 2024There is a growing body of evidence indicating a possible association between genetic variations and attention-deficit hyperactivity disorder (ADHD), although the... (Review)
Review
There is a growing body of evidence indicating a possible association between genetic variations and attention-deficit hyperactivity disorder (ADHD), although the results have been inconsistent. The objective of this study was to evaluate the correlation between the GRIN2A, GRIN2B and GRM7 gene polymorphisms and ADHD. A comprehensive meta-analysis and subgroup evaluation was conducted using a fixed-effects model to analyze the association between ADHD and GRIN2B (rs2284411), GRIN2A (rs2229193), and GRM7 (rs3792452) in six genetic models (dominant, recessive, overdominant, homozygous, heterozygous, and allele models). The meta-analysis comprised 8 studies. The overall analysis showed that the GRIN2B rs2284411 T allele and T carries were significantly associated with a decreased risk of ADHD (dominant model:TT + CT vs. CC: OR = 0.783; 95% CI: 0.627-0.980; = 0.032, allele model:T vs. C: OR = 0.795; 95% CI: 0.656-0.964; = 0.019), especially in the Korean subgroup (dominant model:TT + CT vs. CC: OR = 0.640; 95% CI: 0.442-0.928; = 0.019, overdominant model: CT vs. TT + CC: OR = 0.641; 95% CI: 0.438-0.938; = 0.022, allele model:T vs. C: OR = 0.712; 95% CI: 0.521-0.974; = 0.034 and heterozygous model: CT vs. CC: OR = 0.630; 95% CI: 0.429-0.925; = 0.018). However, no meaningful associations were found for rs2229193 and rs3792452. The results of the meta-analysis provide strong evidence that the rs2284411 T allele is significantly associated with reduced susceptibility to ADHD, particularly in the Korean population.
PubMed: 38544802
DOI: 10.3389/fgene.2024.1348387 -
Medicina (Kaunas, Lithuania) Mar 2024: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma... (Meta-Analysis)
Meta-Analysis Review
: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. : PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). : Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; -value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; -value is 0.008) of the polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; -value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; -value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; -value is 0.04) genotypes were associated with an increased risk of HNC. : The analysis identified two polymorphisms, and , as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations.
Topics: Humans; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Head and Neck Neoplasms; Genotype; Carcinoma; Case-Control Studies; Xeroderma Pigmentosum Group A Protein
PubMed: 38541204
DOI: 10.3390/medicina60030478 -
Journal of Integrative Neuroscience Mar 2024Single-nucleotide polymorphisms (SNPs) in the proprotein convertase subtilisin/kexin type 9 () gene are known to be associated with susceptibility to several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Single-nucleotide polymorphisms (SNPs) in the proprotein convertase subtilisin/kexin type 9 () gene are known to be associated with susceptibility to several cerebrovascular diseases, including ischemic stroke (IS). The aims of this study was to evaluate associations between gene polymorphisms and the risk of IS. Based on previous reports linking PCSK9 SNPs to plasma lipid levels and to atherosclerosis, and to inconsistencies in the reported associations between the SNPs, plasma lipid levels and IS risk, we choose the rs505151, rs529787, and rs17111503 to performe the association analysis.
METHODS
Using multiple databases, all relevant case-control and cohort studies that matched our search criteria were collected. Quality assessment of included studies was performed using the Newcastle-Ottawa Scale. Demographic and genotype data were extracted from each study, and meta-analysis was performed using Stata/MP 17.0. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed and random effects models.
RESULTS
A critical evaluation was conducted on ten case-control studies, involving a total of 2426 cases and 2424 controls. Pooled results from the allelic models indicated the rs505151 G allele (OR: 1.41, 95% CI: 1.06-1.87, = 0.019, I2 = 53.9%) and the rs17111503 A allele (OR: 1.38, 95% CI: 1.22-1.55, < 0.001, I2 = 43.5%) were significantly associated with IS. Study qualities ranged from moderate (n = 4) to good (n = 6). Begg's and Egger's tests results indicated there was no evidence of publication bias in the findings ( > 0.05).
CONCLUSIONS
This meta-analysis demonstrated that G allele variant of rs505151 and A allele variant of rs17111503 were associated with an increased risk of IS. Based on our findings, these SNPs could serve as potential targets for the diagnosis and treatment of IS. The integration of information on genetic polymorphism into IS risk prediction model may be beneficial in routine clinical practice.
Topics: Humans; Ischemic Stroke; Lipids; Polymorphism, Single Nucleotide; Proprotein Convertase 9
PubMed: 38538222
DOI: 10.31083/j.jin2303062 -
Current Issues in Molecular Biology Mar 2024Subjective cognitive decline (SCD) has been described as a probable early stage of dementia, as it has consistently appeared to precede the onset of objective cognitive... (Review)
Review
Subjective cognitive decline (SCD) has been described as a probable early stage of dementia, as it has consistently appeared to precede the onset of objective cognitive impairment. SCD is related to many risk factors, including genetic predisposition for dementia. The Apolipoprotein (APOE) ε4 allele, which has been thoroughly studied, seems to explain genetic risk for SCD only partially. Therefore, we aimed to summarize existing data regarding genetic factors related to SCD, beyond APOE ε4, in order to improve our current understanding of SCD. We conducted a PRISMA systematic search in PubMed/MEDLINE and Embase databases using the keywords "subjective cognitive decline" and "genetic predisposition" with specific inclusion and exclusion criteria. From the 270 articles identified, 16 were finally included for the qualitative analysis. Family history of Alzheimer's disease (AD) in regard to SCD was explored in eight studies, with conflicting results. Other genes implicated in SCD, beyond APOE ε4, were investigated in six studies, which were not strong enough to provide clear conclusions. Very few data have been published regarding the association of polygenic risk for AD and SCD. Thus, many more genes related to AD must be studied, with polygenic risk scores appearing to be really promising for future investigation.
PubMed: 38534745
DOI: 10.3390/cimb46030129 -
Journal of Opioid Management 2024Orthopedic surgical procedures are expected to increase annually, making it imperative to understand the correlations between patient genetic makeup and post-operative...
INTRODUCTION
Orthopedic surgical procedures are expected to increase annually, making it imperative to understand the correlations between patient genetic makeup and post-operative pain levels.
METHODS
We performed a systematic literature review using PubMed and Cochrane databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 299 articles were initially selected, 20 articles remained after title and abstract review, and nine articles were selected for inclusion upon full text review.
RESULTS
Genetic risk factors identified included the A allele of the 5HT2A gene single nucleotide polymorphism, the AA genotype of the ADRB2 gene, the CG genotype of the IL6 gene, the genotypes CT and TT of the NTRK1 gene, genotypes AA and GA of the OPRM gene, and the AA and GA genotypes of the COMT gene. Additional studies in the review discuss statistical significance of other variants of the COMT gene.
CONCLUSION
There have been genetic association studies performed on the patient heterogeneity and its relationship on patient pain levels, but more data need to be collected to understand the clinical utility of stratifying patients based on genomic sequence.
Topics: Humans; Analgesics, Opioid; Genetic Heterogeneity; Genotype; Pain, Postoperative; Orthopedic Procedures
PubMed: 38533718
DOI: 10.5055/jom.0809 -
Pharmacogenetics and Genomics Jul 2024This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal... (Review)
Review
PURPOSE
This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
METHODS
Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957).
RESULTS
Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin.
CONCLUSION
In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.
Topics: Stevens-Johnson Syndrome; Humans; Anticonvulsants; HLA-B15 Antigen; Carbamazepine; Lamotrigine; Genetic Predisposition to Disease; Alleles
PubMed: 38527170
DOI: 10.1097/FPC.0000000000000531