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The Journal of Investigative Dermatology May 2024Prior studies have found associations between atopic dermatitis (AD) and comorbidities, including depression, obesity, asthma, and allergic rhinitis. Although...
Prior studies have found associations between atopic dermatitis (AD) and comorbidities, including depression, obesity, asthma, and allergic rhinitis. Although observational studies often cannot establish robust causality between potential risk factors and AD, Mendelian randomization minimizes confounding when exploring causality by relying on random allelic assortment at birth. In this study, we systematically reviewed 30 Mendelian randomization studies in AD. Body mass index, gut microbial flora, the IL-18 signaling pathway, and gastroesophageal reflux disease were among the causal factors for AD, whereas AD was causal for several medical conditions, including heart failure, rheumatoid arthritis, and conjunctivitis. These insights may improve preventive counseling in AD.
Topics: Humans; Dermatitis, Atopic; Mendelian Randomization Analysis; Risk Factors; Comorbidity; Gastrointestinal Microbiome; Body Mass Index; Gastroesophageal Reflux; Interleukin-18; Genetic Predisposition to Disease
PubMed: 37977498
DOI: 10.1016/j.jid.2023.10.016 -
Frontiers in Endocrinology 2023The relationship of the methylenetetrahydrofolate reductase () gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The relationship of the methylenetetrahydrofolate reductase () gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence.
METHODS
Several databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size.
RESULTS
A total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models.
CONCLUSION
The gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Genetic Predisposition to Disease; East Asian People; Polymorphism, Genetic; Risk Factors; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 37964957
DOI: 10.3389/fendo.2023.1273218 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436 -
The Clinical Respiratory Journal Dec 2023Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in children, but the findings have been inconsistent. To address these discrepancies, we conducted a systematic review and meta-analysis to assess the relationship between IL10 rs1800896 polymorphisms and the susceptibility to pediatric asthma.
METHODS
A literature search was conducted in PubMed, Scopus, Web of Science, and CNKI databases to identify eligible studies through April 2022. Meta-analysis was then performed using five genetic models: dominant, recessive, homozygous, heterozygous, and allele.
RESULTS
A total of 12 studies comprising 1645 cases along with 1447 controls were included in this meta-analysis. It was found that rs1800896 was not associated significantly with susceptibility to childhood asthma in all genetic models investigated. Subgroup analysis based on the ethnic background of the subjects revealed that rs1800896 was significantly linked to a lower risk of pediatric asthma among Asians in the homozygous model (OR = 0.311, 95% CI = 0.152-0.637, P = 0.001) and in the recessive model (OR = 0.585, 95% CI = 0.405-0.846, P = 0.004), whereas no significant relationship was observed in Egyptians (P > 0.05).
CONCLUSION
In conclusion, IL10 rs1800896 polymorphism may be useful as a predictive marker for childhood asthma in Asians, although further studies are needed to validate the study results.
Topics: Child; Humans; Interleukin-10; Genetic Predisposition to Disease; Polymorphism, Genetic; Asthma; Polymorphism, Single Nucleotide
PubMed: 37937689
DOI: 10.1111/crj.13714 -
Scientific Reports Nov 2023Migraine is a complex disorder with multigenic inheritance and is characterized by the cardinal symptom of unilateral headache. Many genes are responsible for increasing... (Meta-Analysis)
Meta-Analysis
Migraine is a complex disorder with multigenic inheritance and is characterized by the cardinal symptom of unilateral headache. Many genes are responsible for increasing the susceptibility of disease within different populations. Therefore, our primary aim in this review was to catalog the many genes that have been studied in India and after collecting the necessary information, we calculated a more precise risk relationship between an identified variation and migraine. The gene and its associated risk variant were discovered in the Indian population using a PRISMA-based systematic literature review guideline from online databases such as PubMed & Google Scholar. We constructed pooled odds ratios with 95% confidence intervals using multiple genetic models. Also, we looked for heterogeneity using Cochran's Q Test and the I2 statistic. Publication bias was analyzed using Begg's and Egger's tests. A p-value less than 0.05 was judged to be statistically significant for all tests. After a critical analysis, a total of 24 studies explored about 21 genes with 31 variants out of which only nine genes have been studied more than two times in the Indian population and thus were found eligible for the meta-analysis. It has been found, that the ACE-DD variant (allele model: OR: 1.37 [1.11-1.69], I = 0%/ fixed model), ESR1-PvuII (allele model: OR: 1.47 [1.24-1.74], I = 0%/ fixed model) significantly increases the risk of migraine in Indian population. Also, a protective role of the LRP1-rs11172113variant was observed for both migraine and its clinical subtype i.e., MA (allelic model: OR of 0.65 [0.50-0.83] I = 44% and allele: OR: 0.54 [0.37-0.78], I = 52%) respectively. Overall, the results of this meta-analysis indicated that the ACE-DD variant and the ESR1-PvuII were associated with an increased risk of migraine in the Indian community, while the LRP1-rs11172113 variant was associated with protection from migraine in this population.
Topics: Humans; Genetic Predisposition to Disease; Migraine Disorders; Genetic Association Studies; Alleles; Asian People
PubMed: 37925562
DOI: 10.1038/s41598-023-45531-3 -
Tropical Medicine and Infectious Disease Sep 2023The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy... (Review)
Review
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against infection. However, recent studies suggest that this microorganism's evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria.
PubMed: 37888591
DOI: 10.3390/tropicalmed8100463 -
Frontiers in Immunology 2023Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were...
INTRODUCTION
Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were performed with application of serological methods or low resolution genetic typing, which led to inconsistent results even among the same population. The present review is intended to summarize the state-of-art knowledge on the HLA significance in GD and GO in Asians and Caucasians, as well as to find the most significant alleles for each of the populations.
METHODS
PubMed was searched for relevant articles using the following search terms: HLA plus thyroid-associated ophthalmopathy or Graves' disease or Graves' orbitopathy or thyroid eye disease or thyroid-associated orbitopathy.
RESULTS
In Asian population GD was found to be associated mostly with , , , , , and , while , , are potentially protective. can be considered associated with increased risk of GO in Asians, while may play protective role. In Caucasians, , , are associated with GD risk while , may be protective. Significance of HLA in the course of GD and novel aspects of HLA amino acid variants and potential HLA-based treatment modalities were also discussed.
Topics: Humans; Graves Ophthalmopathy; HLA-DQ Antigens; HLA-DRB1 Chains; Haplotypes; Graves Disease; HLA-B Antigens
PubMed: 37841270
DOI: 10.3389/fimmu.2023.1256922 -
Journal of Orthopaedic Surgery and... Oct 2023Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis.
OBJECTIVES
We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility.
METHODS
All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI).
RESULTS
The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population.
CONCLUSION
We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.
Topics: Female; Humans; Male; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Growth Differentiation Factor 5; Osteoarthritis, Hip; Osteoarthritis, Knee; Polymorphism, Single Nucleotide
PubMed: 37817264
DOI: 10.1186/s13018-023-04245-y -
Neurology and Therapy Dec 2023Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most... (Review)
Review
Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.
INTRODUCTION
Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most advanced therapeutic approach at present. Three drugs (lecanemab, donanemab and aducanumab) are on track to be marketed in the coming months. In this systematic review, we review all Phase 2 and Phase 3 clinical trials conducted in this indication and the particularities of the molecules tested.
METHODS
The PubMed and ClinicalTrials.gov databases were searched through February 2023 for Phase 2 and 3 clinical trials involving passive anti-amyloid or anti-tau immunotherapies with published results. This review has been compiled in compliance with the PRISMA checklists.
RESULTS
Of the 165 studies found and after eliminating duplicates, 40 studies had their results published on PubMed and/or ClinicalTrials.gov. Eight anti-amyloid molecules and four anti-tau molecules were the subject of Phase 2 studies, seven anti-amyloids were the subject of Phase 3 trials, and two molecules were granted early marketing approval by the US Food and Drug Administration (FDA). The results were compiled in summary tables showing the primary endpoints used, results, age of the study population and specific adverse events for these molecules.
DISCUSSION
Passive immunotherapy in AD is largely dominated by anti-amyloid antibodies, which are more numerous and more advanced in the pipeline. Lecanemab, donanemab and aducanumab are distinguished by their relative efficacy in terms of cognitive and functional evaluation but also by a decrease in amyloid and tau proteins in the brain. These three molecules have in common that they bind to N-terminal ends of amyloid fibrils and plaques. The findings of their studies raise the question of which criteria to apply when choosing which patient will receive them when marketed, such as the apoliprotein E gene's fourth allele (APOE4) genetic status of patients. The large number of negative studies may also raise the question of the criteria for defining the disease and the possible interest in redefining it on biological grounds to offer a more personalized medicine to patients suffering from neurodegenerative diseases.
PubMed: 37812325
DOI: 10.1007/s40120-023-00541-1 -
Annals of Medicine and Surgery (2012) Oct 2023Our meta-analysis aims to explore the association of two single nucleotide variants; rs9939609 and rs8050136, within the FTO gene with risk of pulmonary tuberculosis... (Review)
Review
OBJECTIVE
Our meta-analysis aims to explore the association of two single nucleotide variants; rs9939609 and rs8050136, within the FTO gene with risk of pulmonary tuberculosis (PTB).
METHODS
The association of two single nucleotide variants with PTB in three genetic models was evaluated using pooled odds ratios (ORs) with 95% CIs.
RESULTS
No significant association was observed between the rs9939609 polymorphism and PTB when assuming an allelic model (OR: 1.10; 95% CI: 0.85-1.41; =0.47; I = 64.98%), a recessive model (OR: 2.04; 95% CI: 0.87-4.77; =0.10; I = 67.18%), or a dominant model (OR: 0.96; 95% CI: 0.83-1.11; =0.56; I = 27.45%). Likewise, no association was observed between rs8050136 polymorphism and PTB when assuming allelic model (OR: 1.17; 95% CI: 0.87-1.58; =0.31; I = 64.20%) or recessive model (OR: 1.04; 95% CI: 0.32-3.38; =0.95; I = 68.82%) or dominant model (OR: 1.22; 95% CI: 0.87-1.71; =0.26; I = 58.69%).
CONCLUSION
There might be no association between the rs9939609 and rs8050136 variants in the FTO gene, and the risk of PTB.
PubMed: 37811091
DOI: 10.1097/MS9.0000000000001188