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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 -
International Ophthalmology Jan 2022Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and vascular structures and is reported to be significantly influenced by inflammation and inflammatory mediators like cytokines. In this study, a systematic review and meta-analysis were performed to analyze the association between cytokine gene polymorphisms and DR.
METHODS
We identified relevant studies from Scopus, PubMed, and Google scholar databases. Allele and genotype frequencies were pooled. Heterogeneity and publication bias were explored. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the relation.
RESULTS
A total of 3337 cases and 4945 controls in 19 eligible studies were included in the meta-analysis. Overall, results indicated the negative association between the cytokine gene polymorphisms and DR susceptibility in the allelic model (IFN-γ (rs2430561): OR 0.64, [CI]: 0.5 to 0.82; and TGF-β (rs1800471): [OR] = 0.15, [CI]: 0.03 to 0.79); and also, in the dominant model (IFN-γ (rs2430561): OR = 0.4, [CI]: 0.22 to 0.75; and TGF-β (rs1800471): OR = 0.14, [CI]: 0.05 to 0.4).
CONCLUSION
The present study suggests that IFN-γ (rs2430561) and TGF-β (rs1800471) polymorphisms are associated with decreased susceptibility to DR.
Topics: Cytokines; Diabetes Mellitus; Diabetic Retinopathy; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Polymorphism, Single Nucleotide
PubMed: 34432176
DOI: 10.1007/s10792-021-02011-9 -
Otolaryngology--head and Neck Surgery :... Jun 2023The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this meta-analysis is to evaluate the impact of genetic polymorphisms on platinum-based chemotherapy (PBC)-induced ototoxicity.
DATA SOURCES
Systematic searches of PubMed, Embase, Cochrane, and Web of Science were conducted from the inception of the databases to May 31, 2022. Abstracts and presentations from conferences were also reviewed.
REVIEW METHODS
Four investigators independently extracted data in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Differences in the prevalence of PBC-induced ototoxicity between reference and variant (i) genotypes and (ii) alleles were analyzed. The overall effect size was presented using the random-effects model as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
From 32 included articles, 59 single nucleotide polymorphisms on 28 genes were identified, with 4406 total unique participants. For allele frequency analysis, the A allele in ACYP2 rs1872328 was positively associated with ototoxicity (OR: 2.61; 95% CI: 1.06-6.43; n = 2518). Upon limiting to cisplatin use only, the T allele of COMT rs4646316 and COMT rs9332377 revealed significant results. For genotype frequency analysis, the CT/TT genotype in ERCC2 rs1799793 demonstrated an otoprotective effect (OR: 0.50; 95% CI: 0.27-0.94; n = 176). Excluding studies using carboplatin or concomitant radiotherapy revealed significant effects with COMT rs4646316, GSTP1 rs1965, and XPC rs2228001. Major sources of variations between studies include differences in patient demographics, ototoxicity grading systems, and treatment protocols.
CONCLUSION
Our meta-analysis presents polymorphisms that exert ototoxic or otoprotective effects in patients undergoing PBC. Importantly, several of these alleles are observed at high frequencies globally, highlighting the potential for polygenic screening and cumulative risk evaluation for personalized care.
Topics: Humans; Antineoplastic Agents; Ototoxicity; Platinum; Cisplatin; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein; Acid Anhydride Hydrolases
PubMed: 36802061
DOI: 10.1002/ohn.222 -
Expert Review of Gastroenterology &... 2015We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility.
METHODS
PubMed and Web of Science databases were searched (to June 2015) on IL18RAP rs917997 and CCR3 rs6441961 polymorphisms.
RESULTS
The meta-analysis included 16 and 7 studies for rs917997 and rs6441961, respectively. The minor risk A allele at both rs917997 and rs6441961 carried risks (odds ratios) of 1.24 (95% CI 1.18-1.31) and 1.21 (95% CI 1.12-1.31), respectively. These alleles contributed to increase risks in all celiac disease patients by 5.04 and 6.35%. The estimated lambdas were 0.73 and 0.51, suggesting that an additive model would be the best choice for both gene effects.
CONCLUSIONS
This meta-analysis provides robust estimates that IL18RAP rs917997 and CCR3 rs6441961 are potential risk factors for celiac disease in European populations. Studies are needed to confirm these findings in different ethnicities.
Topics: Celiac Disease; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-18 Receptor beta Subunit; Polymorphism, Single Nucleotide; Receptors, CCR3; Risk Factors; White People
PubMed: 26289103
DOI: 10.1586/17474124.2015.1075880 -
Clinical and Investigative Medicine.... Dec 2016A meta-analysis was preformed to determine which HLA-DRB1 alleles are associated with increased risk of rheumatoid arthritis (RA) in Asian patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
A meta-analysis was preformed to determine which HLA-DRB1 alleles are associated with increased risk of rheumatoid arthritis (RA) in Asian patients.
METHODS
Medline, PubMed, Central, EMBASE, Cochrane, and Google Scholar databases were searched until November 3, 2015 using the following keywords: rheumatoid arthritis; RA, HLA-DRB1; severity; treatment; and, prognosis. Randomized-controlled-trials, prospective, retrospective, cohort and case-controlled studies that examined the HLA-DRB1 allelic association with RA in Asians were included. The frequencies of allelic types and the shared epitope (SE) were compared between patients with or without RA.
RESULTS
A total of 331 articles were identified after duplicates removed, and 40 studies, with 5470 RA patients and 5837 control patients, were included in the analysis. Pooled odds ratios (ORs) revealed the frequencies of HLA-DRB1*04 and *10 were higher in the RA group, and the frequency of *14 was lower in the RA group as compared to controls (*04: OR = 3.35, 95% CI: 2.28-3.99, p < .001; *10: OR = 2.08, 95% CI: 1.55-2.78, p < .001; *14: OR = 0.70, 95% CI: 0.54-0.90, p = .006). No associations were noted for *01 and *09. Pooled ORs revealed associations of *0101 (OR = 1.58), *0401 (OR = 2.17), *0404 (OR = 1.91), *0405 (OR = 3.73), *0410 (OR = 2.24), *1001 (OR = 1.78) and SE positive (OR = 2.38) with RA. HLA-DRB1 *14 subtypes did not show associations with RA.
CONCLUSIONS
HLA-DRB1 allelic variations are associated with RA in Asian patients.
Topics: Alleles; Arthritis, Rheumatoid; Asian People; Epitopes; Female; HLA-DRB1 Chains; Humans; Male; Polymorphism, Genetic
PubMed: 27917778
DOI: 10.25011/cim.v39i6.27487 -
BMJ (Clinical Research Ed.) Sep 2016To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.
DESIGN
Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.
DATA SOURCES
Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.
RESULTS
We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.
CONCLUSIONS
We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015015969.
Topics: Adiposity; Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Genetic Predisposition to Disease; Genotype; Humans; Obesity; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 27650503
DOI: 10.1136/bmj.i4707 -
Scientific Reports Nov 2014Human leukocyte antigen (HLA)-DR4/HLA-DRB1*04 has been reported to be a risk factor for Vogt-Koyanagi-Harada disease (VKH) with various strength of association. Its... (Meta-Analysis)
Meta-Analysis Review
Human leukocyte antigen (HLA)-DR4/HLA-DRB1*04 has been reported to be a risk factor for Vogt-Koyanagi-Harada disease (VKH) with various strength of association. Its sub-alleles were also found to be associated with VKH. However the results were inconsistent. In this study, we systematically searched the related literature, pooled the odds ratios (ORs) and 95% confidence interval (CI) of association of HLA-DR4/HLA-DRB1*04 or its sub-alleles with VKH from individual studies, and explored the potential source of heterogeneity. A total of 1853 VKH patients and 4164 controls from 21 articles were included in this meta-analysis. The pooled OR of association of HLA-DR4/HLA-DRB1*04 and VKH was 8.42 (95% CI: 5.69-12.45). There were significant heterogeneity (I(2) = 71%). Subgroup analysis indicated that ethnicity was the source of heterogeneity (all I(2) = 0, ORs ranged from 2.09-13.69 in subgroups). The sub-alleles, HLA-DRB1*0404 (OR = 2.57), 0405 (OR = 10.31) and 0410 (OR = 6.52) increased the risk of VKH; 0401 (OR = 0.21) protected VKH; while other sub-alleles were not associated with VKH. Our meta-analysis confirmed the association between VKH and HLA-DR4/DRB1*04, found the strength of association is different in different ethnic groups, and identified HLA-DRB1*0404, 0405 and 0410 as risk sub-alleles while 0401 as protective sub-allele.
Topics: Alleles; Case-Control Studies; Genetic Association Studies; Genetic Predisposition to Disease; HLA-DR4 Antigen; Humans; Odds Ratio; Uveomeningoencephalitic Syndrome
PubMed: 25382027
DOI: 10.1038/srep06887 -
Clinical Genetics Feb 2017The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. However, the results of these studies were... (Meta-Analysis)
Meta-Analysis Review
The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. However, the results of these studies were inconsistent, especially when conducted in different populations. Therefore, we performed the current study to systematically review the broad spectrum of genetic polymorphisms that were suspected to be involved in RM, and discussed potential genetic biomarkers of RM. Eligible articles were identified in PubMed, Medline, Embase and CNKI. Odd ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association, and a probability value (p value) of 0.05 or less was considered as statistically significant. A total of 425 eligible articles were included in this systematic review and 369 articles evaluating 124 polymorphisms of 73 genes were meta-analyzed. Significant associations were found between RM and 53 genetic polymorphisms of 37 genes. Our findings suggest that genetic variants of HLA-G, IFNG, TNF, IL-6, IL-10, FII, FV, FXIII, ITGB3, MTR, MTHFR, PAI-1, NOS3, KDR, TP53, VEGFA, CYP17, CYP1A1, CYP2D6, ANXA5, and XCI may serve as biological markers of RM. This study indicates that over-active immunological responses, thrombophilia, abnormal placental function, and disturbance of metabolic regulation may be implicated in the pathogenesis of RM.
Topics: Abortion, Habitual; Alleles; Biomarkers; Female; Genetic Predisposition to Disease; Genotype; Humans; Maternal Inheritance; Polymorphism, Genetic; Pregnancy
PubMed: 27792840
DOI: 10.1111/cge.12910 -
Infection, Genetics and Evolution :... Sep 2016The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp... (Meta-Analysis)
Meta-Analysis Review
The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta-analysis study that provides a descriptive study of the distribution of CCR5-delta32 allele in Brazilian population.
Topics: Brazil; Gene Frequency; Genetic Association Studies; Humans; Receptors, CCR5; Risk Factors; White People
PubMed: 27208805
DOI: 10.1016/j.meegid.2016.05.024 -
Human Immunology May 2015The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent... (Meta-Analysis)
Meta-Analysis Review
PROBLEM
The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM).
METHOD OF STUDY
A systematic literature search was performed for studies that evaluated the association between HLA alleles, HLA sharing and RM. RM was defined as three or more consecutive unexplained miscarriages and a control group was included of women with at least one live birth and no miscarriages in their history. Meta-analyses were performed and the pooled odds ratio (OR) was calculated.
RESULTS
We included 41 studies. Selection bias was present in 40 studies and information bias in all studies. Meta-analyses showed an increased risk of RM in mothers carrying a HLA-DRB1*4 (OR 1.41, 95% CI 1.05-1.90), HLA-DRB1*15 (OR 1.57, 95% CI 1.15-2.14), or a HLA-E*01:01 allele (OR 1.47, 95% CI 0.20-1.81), and a decreased risk with HLA-DRB1*13 (OR 0.63, 95% CI 0.45-0.89) or HLA-DRB1*14 (OR 0.54, 95% CI 0.31-0.94). Pooling results for HLA sharing showed that HLA-B sharing (OR 1.39, 95% CI 1.11-1.75) and HLA-DR sharing (OR 1.57, 95% CI 1.10-1.25) were both associated with the occurrence of RM.
CONCLUSION
Although the present systematic review and meta-analysis demonstrates that specific HLA alleles and HLA sharing are associated with RM, a high degree of bias was present and therefore observed results should be interpreted carefully.
Topics: Abortion, Habitual; Alleles; Female; Genetic Association Studies; HLA-B Antigens; HLA-DRB1 Chains; Histocompatibility; Histocompatibility Antigens Class I; Humans; Pregnancy; Risk; Selection Bias; HLA-E Antigens
PubMed: 25700963
DOI: 10.1016/j.humimm.2015.02.004