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Cureus Jun 2023Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the genetic factors involved in the development of BP. The connection between major histocompatibility complex class II, specifically HLA-DQA1, and BP remains inconclusive. The objective of this review is to find potential associations between BP and HLA-DQA1 alleles, identify the HLA-DQA1 alleles associated with an increased or decreased risk of developing BP, and highlight literature gaps for future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to conduct a literature review. Databases used included PubMed/MEDLINE, Google Scholar, Embase, and Cochrane Library. Only studies written in English and conducted after 2000 that investigated the association between HLA-DQA1 and BP in human subjects were included. Odds ratios were calculated from the data provided in the studies, and a meta-analysis was conducted using Review Manager (The Cochrane Collaboration, London, United Kingdom) and MetaXL (EpiGear International Pty Ltd., Queensland, Australia) software. The systematic review found five eligible studies, and all were included in the meta-analysis. Results show an increased odds for BP in the HLA-DQA1*05:05 loci (odds ratio (OR) = 2.25; 95% confidence interval (CI) = 1.80, 2.80) and decreased odds for BP in the HLA-DQA1*02:01 loci (OR = 0.50; 95% CI = 0.36, 0.70). Further research is needed to confirm these findings and explore the potential clinical implications for personalized medicine approaches in BP patients.
PubMed: 37416040
DOI: 10.7759/cureus.39923 -
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 -
Frontiers in Cardiovascular Medicine 2022Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are...
BACKGROUND
Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles.
METHODS AND RESULTS
By searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites.
CONCLUSION
The rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.
PubMed: 36158791
DOI: 10.3389/fcvm.2022.946289 -
F1000Research 2022In-stent restenosis (ISR) remains a major drawback in coronary stenting. The association between the CYP2C19 loss of function (LOF) gene and the prevalence of ISR after...
In-stent restenosis (ISR) remains a major drawback in coronary stenting. The association between the CYP2C19 loss of function (LOF) gene and the prevalence of ISR after coronary stenting remains controversial. Previous studies have produced conflicting results and have been limited by their small population sizes. We conducted this systematic review and meta-analysis to determine the association between the presence of the CYP2C19 LOF gene and the prevalence of ISR. A systematic online database search was performed until April 2021. The primary outcome was ISR and assessed using OR with 95% CI. Publication bias was assessed using the Newcastle Ottawa Scale. was applied to examine heterogeneities among the studies. A total of 284 patients (four non-randomized controlled trial studies) were included in this study. Two hundred and six patients had wild-type genotypes, while 78 patients had the LOF genotype. Among the 78 patients with the LOF gene, 40 patients had an ISR. Meanwhile, of the 206 patients with a wild-type gene, 69 patients had an ISR. The LOF gene was associated with a higher risk of ISR (OR 95% CI = 2.84 [1.54-5.24], = 0.0008). A major limitation in our study was the small number of previous studies and small sample sizes. Patients with LOF genes, regardless of the allele variation, treated with clopidogrel, had a higher risk of developing ISR after coronary stenting.
PubMed: 38721014
DOI: 10.12688/f1000research.109321.2 -
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 -
Frontiers in Genetics 2023Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect of and...
Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect of and gene polymorphisms on COPD risk has not been fully characterized. To investigate the association of and polymorphisms with COPD risk. A systematic search was conducted on 9 databases to identify studies published in English and Chinese. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines (PRISMA). The pooled OR and 95% CI were calculated to evaluate the association of and polymorphisms with COPD risk. The I test, Q test, Egger's test, and Begg's test were conducted to determine the level of heterogeneity and publication bias of the included studies. In total, 857 articles were retrieved, among which 59 met the inclusion criteria. The rs1051740 polymorphism (homozygote, heterozygote, dominant, recessives, and allele model) was significantly associated with high risk of COPD risk. Subgroup analysis revealed that the rs1051740 polymorphism was significantly associated with COPD risk among Asians (homozygote, heterozygote, dominant, and allele model) and Caucasians (homozygote, dominant, recessives, and allele model). The rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with a low risk of COPD. Subgroup analysis showed that the rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Asians. The rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk. Subgroup analysis showed that the rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk among Caucasians. The rs1138272 polymorphism (heterozygote and dominant model) was significantly associated with COPD risk. Subgroup analysis suggested that the rs1138272 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Caucasians. The C allele in rs1051740 among Asians and the CC genotype among Caucasians may be risk factors for COPD. However, the GA genotype in rs2234922 may be a protective factor against COPD in Asians. The GG genotype in rs1695 and the TC genotype in rs1138272 may be risk factors for COPD, especially among Caucasians.
PubMed: 37284064
DOI: 10.3389/fgene.2023.1128985 -
Schizophrenia Bulletin Sep 2022Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental risk factors for schizophrenia, but it is unclear if schizophrenia genetic risk alleles contribute to this association.
STUDY DESIGN
In this systematic review and meta-analysis, we assessed the evidence for gene-environment correlation (genes influence likelihood of environmental exposure) between schizophrenia polygenic risk score (PRS) and reported childhood adversity. We also assessed the evidence for a gene-environment interaction (genes influence sensitivity to environmental exposure) in relation to the outcome of schizophrenia and/or psychosis. This study was registered on PROSPERO (CRD42020182812). Following PRISMA guidelines, a search for relevant literature was conducted using Cochrane, MEDLINE, PsycINFO, Web of Science, and Scopus databases until February 2022. All studies that examined the association between schizophrenia PRS and childhood adversity were included.
STUDY RESULTS
Seventeen of 650 identified studies met the inclusion criteria and were assessed against the Newcastle-Ottawa Scale for quality. The meta-analysis found evidence for gene-environment correlation between schizophrenia PRS and childhood adversity (r = .02; 95% CI = 0.01, 0.03; P = .001), but the effect was small and therefore likely to explain only a small proportion of the association between childhood adversity and psychosis. The 4 studies that investigated a gene-environment interaction between schizophrenia PRS and childhood adversity in increasing risk of psychosis reported inconsistent results.
CONCLUSIONS
These findings suggest that a gene-environment correlation could explain a small proportion of the relationship between reported childhood adversity and psychosis.
Topics: Adverse Childhood Experiences; Child; Gene-Environment Interaction; Humans; Multifactorial Inheritance; Risk; Schizophrenia
PubMed: 35674151
DOI: 10.1093/schbul/sbac049 -
Journal of Personalized Medicine Sep 2021Although gene polymorphisms may be associated with the plasma lipid concentration, the literature has not shown a consistent pattern. In this study, we attempted to... (Review)
Review
BACKGROUND
Although gene polymorphisms may be associated with the plasma lipid concentration, the literature has not shown a consistent pattern. In this study, we attempted to elucidate the association between the 69C>T, 825V>I, and 230R>C polymorphisms and the plasma lipid concentration through a systematic review and meta-analysis.
METHODS
We selected studies published up to October 2020 in the PubMed, Web of Science, and Embase databases according to inclusion and exclusion criteria. The mean difference (MD) and 95% confidence interval (CI) were used to assess the relationship between the presence of 69C>T, 825V>I, and 230R>C and plasma lipid levels. Meta-analysis was performed using Review Manager (version 5.3). Both Begg's test and Egger's regression test of the funnel plot were performed using R Studio software (version 3.6.0) to identify publication bias.
RESULTS
We analyzed the data on the 69C>T polymorphism involving 14,843 subjects in 11 studies, 825V>I polymorphism involving 2580 subjects in 5 studies, and 230R>C polymorphism involving 4834 subjects in 4 studies. The T allele carriers in 69C>T, II carriers in 825V>I, and C carriers in 230R>C had lower high-density lipoprotein cholesterol levels; the MD (95% CI) was -0.05 mmol/L (95% CI: -0.09 to -0.01, = 0.02), -0.05 mmol/L (95% CI: -0.09 to -0.00, = 0.03), and -0.1 mmol/mL (95% CI: -0.12 to -0.07 mmol/L, < 0.00001), respectively. In the case of 230R>C, the serum total cholesterol concentration of C carriers was significantly lower than that of RR carriers (-0.2 mmol/L, 95% CI: -0.3 to -0.11, < 0.0001).
CONCLUSION
This meta-analysis demonstrates that the 69C>T, 825V>I, and 230R>C polymorphisms could affect the plasma lipid concentration. As the plasma lipid concentration may be related to various diseases, genotyping could be useful for the management of lipid levels.
PubMed: 34575660
DOI: 10.3390/jpm11090883 -
Pain Physician Sep 2023Responsiveness to opioid analgesics differs among patients with acute postoperative pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Responsiveness to opioid analgesics differs among patients with acute postoperative pain.
OBJECTIVE
Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids.
STUDY DESIGN
An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain.
METHODS
PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021.
RESULTS
Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human μ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms.
LIMITATIONS
Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis.
CONCLUSIONS
In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia.
KEY WORDS
Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Topics: Humans; Analgesics, Opioid; Catechol O-Methyltransferase; Cytochrome P-450 CYP3A; Pain, Postoperative; Polymorphism, Single Nucleotide
PubMed: 37774182
DOI: No ID Found -
BMC Cardiovascular Disorders Aug 2022Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and...
BACKGROUND
Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically.
METHODS
We searched MEDLINE via Ovid, Embase, PubMed, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case-control, prospective cohort, nested case-control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031.
RESULTS AND DISCUSSION
We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration.
Topics: Cardiovascular Diseases; Cross-Sectional Studies; Diet; Humans; Myocardial Infarction; Prospective Studies
PubMed: 35987633
DOI: 10.1186/s12872-022-02808-1