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PloS One 2015Studies investigating the influence of toll-like receptor (TLR) polymorphisms and tuberculosis susceptibility have yielded varying and often contradictory results in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies investigating the influence of toll-like receptor (TLR) polymorphisms and tuberculosis susceptibility have yielded varying and often contradictory results in different ethnic groups. A meta-analysis was conducted to investigate the relationship between TLR variants and susceptibility to tuberculosis, both across and within specific ethnic groups.
METHODS
An extensive database search was performed for studies investigating the relationship between TLR and tuberculosis (TB) susceptibility. Data was subsequently extracted from included studies and statistically analysed.
RESULTS
32 articles involving 18907 individuals were included in this meta-analysis, and data was extracted for 14 TLR polymorphisms. Various genetic models were employed. An increased risk of TB was found for individuals with the TLR2 rs3804100 CC and the TLR9 rs352139 GA and GG genotypes, while decreased risk was identified for those with the AG genotype of TLR1 rs4833095. The T allele of TLR6 rs5743810 conferred protection across all ethnic groups. TLR2 rs5743708 subgroup analysis identified the A allele to increase susceptibility to TB in the Asian ethnic group, while conferring protection in the Hispanic group. The T allele of TLR4 rs4986791 was also found to increase the risk of TB in the Asian subgroup. All other TLR gene variants investigated were not found to be associated with TB in this meta-analysis.
DISCUSSION
Although general associations were identified, most TLR variants showed no significant association with TB, indicating that additional studies investigating a wider range of pattern recognition receptors is required to gain a better understanding of this complex disease.
Topics: Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Toll-Like Receptors; Tuberculosis
PubMed: 26430737
DOI: 10.1371/journal.pone.0139711 -
Environmental Health and Preventive... Nov 2017The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya intracranial artery stenosis/occlusion disease (ICASO) recently. However, the effect sizes of p.R4810K were in great discrepancy even in studies of the same ethnic population and firm conclusions of other rare variants have been elusive given the small sample sizes and lack of replication. Thus, we performed this study to quantitatively evaluate whether or to what extent the rare variants of RNF213 contribute to MMD and ICASO in different populations.
METHODS
A systematic search of PubMed, EMBASE, ISI web of science, CNKI, and WANFANG DATA was conducted up to 5 September 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity and family history. Sensitivity and publication bias analysis were performed to test the robustness of associations. All the statistical analyses were conduct using STATA 12.0.
RESULTS
Twenty studies including 2353 MMD cases and 5488 controls and 11 studies including 1778 ICASO cases and 3140 controls were included in this study. Pooled ORs indicated that RNF213 p.R4810K significantly increased MMD and ICASO risk in East Asians with great effect sizes of discrepancy (dominant model: odds ratios 184.04, 109.77, and 31.53 and 10.07, 28.52, and 5.59 for MMD and ICASO, respectively, in Japan, Korea, and China). It significantly increased familial MMD risk in Japan, Korea, and China with 5 ~ 36 times larger effect sizes than that for sporadic ones in each country (dominant model ORs 1802.44, 512.42, 1109.02 and 134.35, 99.82, and 30.52, respectively, for familial and sporadic cases). The effect sizes of RNF213 p.R4810K to sporadic MMD were 3 ~ 4 times larger in Japan and Korea than those in China. RNF213 p.R4810K also increased the ICASO risk in Japan and Korea with 2 ~ 4 times larger effect sizes than that in China (dominant model ORs 10.71, 28.52, and 5.59, respectively). Another two rare variants- p.E4950D and p.A5021V significantly increased MMD risk in Chinese population (dominant model ORs 9.06 and 5.01, respectively). Various other rare variants in RNF213 were identified in Japanese, Chinese, European, and Hispanic American populations without association evidence available yet.
CONCLUSIONS
This meta-analysis shows the critical roles of RNF213 p.R4810K in MMD especially familial MMD and ICASO in Japan, Korea, and China. Except for RNF213 p.R4810K, MMD seems to have more complex determiners in China. Distinct genetic background exists and other environmental or genetic factor(s) may contribute to MMD. Studies focused on delineating the ethnicity-specific factors and pathological role of RNF213 variants in MMD and ICASO are needed.
Topics: Adenosine Triphosphatases; Arterial Occlusive Diseases; Carotid Artery Diseases; Constriction, Pathologic; Genetic Predisposition to Disease; Genetic Variation; Humans; Moyamoya Disease; Ubiquitin-Protein Ligases
PubMed: 29165161
DOI: 10.1186/s12199-017-0680-1 -
Medicine Dec 2014Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for... (Meta-Analysis)
Meta-Analysis Review
Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.
Topics: Amino Acid Substitution; Asian People; Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Liver Neoplasms; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein
PubMed: 25546681
DOI: 10.1097/MD.0000000000000330 -
Frontiers in Immunology 2021Allergic diseases (atopic dermatitis, food allergy, eosinophilic esophagitis, asthma and allergic rhinitis), perhaps more than many other traditionally grouped...
Allergic diseases (atopic dermatitis, food allergy, eosinophilic esophagitis, asthma and allergic rhinitis), perhaps more than many other traditionally grouped disorders, share several overlapping inflammatory pathways and risk factors, though we are still beginning to understand how the relevant patient and environmental factors uniquely shape each disease. Precision medicine is the concept of applying multiple levels of patient-specific data to tailor diagnoses and available treatments to the individual; ideally, a patient receives the right intervention at the right time, in order to maximize effectiveness but minimize morbidity, mortality and cost. While precision medicine in allergy is in its infancy, the recent success of biologics, development of tools focused on large data set integration and improved sampling methods are encouraging and demonstrates the utility of refining our understanding of allergic endotypes to improve therapies. Some of the biggest challenges to achieving precision medicine in allergy are characterizing allergic endotypes, understanding allergic multimorbidity relationships, contextualizing the impact of environmental exposures (the "exposome") and ancestry/genetic risks, achieving actionable multi-omics integration, and using this information to develop adequately powered patient cohorts and refined clinical trials. In this paper, we highlight several recently developed tools and methods showing promise to realize the aspirational potential of precision medicine in allergic disease. We also outline current challenges, including exposome sampling and building the "knowledge network" with multi-omics integration.
Topics: Allergens; Animals; Biomarkers; Computational Biology; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genomics; Humans; Hypersensitivity; Machine Learning; Phenotype; Precision Medicine; Proteomics
PubMed: 34484229
DOI: 10.3389/fimmu.2021.720746 -
Pharmacological Research Jul 2022Cannabis sativa is a recreational drug commonly consumed in Europe and is getting popularity for both recreational and therapeutic use. In some individuals, the use of... (Review)
Review
OBJECTIVE
Cannabis sativa is a recreational drug commonly consumed in Europe and is getting popularity for both recreational and therapeutic use. In some individuals, the use of cannabis leads to psychotic disorders. This systematic review summarizes the current evidence linking genetic polymorphisms and inter-individual susceptibility to psychosis induced by cannabis.
METHOD
Studies published from 2005 to 2020 were identified through Medline using PubMed, Web of Science and Scopus database and searches were conducted according to PRISMA guidelines. Initial search was performed with terms: "cannabis induced psychosis" AND "genetics".
RESULTS
From the initial group of 108 papers, 18 studies met our inclusion criteria. Many of the findings revealed associations with genetic polymorphisms modulations of genes involved directly (COMT, DRD2 and DAT) or indirectly (AKT1) to dopamine pathways. The most consistent finding was with COMT rs4680, where the presence of the Val allele was associated with a higher risk for cannabis-induced psychosis. This higher susceptibility was also reported for AKT1 (rs2494732) with the CC genotype. Of note, the only genome-wide association study identified a significant signal close to the cholinergic receptor muscarinic 3 represented by rs115455482 and rs74722579 predisposing to cannabis-induced hallucinations and remarkably no dopaminergic target was found.
CONCLUSION
Actual evidence supports the role of dopamine in cannabis induced psychosis. However, most of genetic polymorphism studies have as a starting point the pre-existing dopaminergic theoretical basis for psychosis. This alerts to the importance of more broad genetic studies. Integrate genetic results into biological systems may enhance our knowledge of cannabis induced psychosis and could help in the prevention and treatment of these patients.
Topics: Cannabis; Catechol O-Methyltransferase; Dopamine; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Marijuana Abuse; Polymorphism, Single Nucleotide; Psychotic Disorders
PubMed: 35588917
DOI: 10.1016/j.phrs.2022.106258 -
Scientific Reports Mar 2021Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus... (Meta-Analysis)
Meta-Analysis
Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05-1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21-2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.
Topics: COVID-19; Disease Susceptibility; HIV Infections; Humans; SARS-CoV-2
PubMed: 33737527
DOI: 10.1038/s41598-021-85359-3 -
World Journal of Surgical Oncology Apr 2022Numerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility.
MATERIALS AND METHOD
Relevant studies were extracted from the electronic databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CMB) up to April 2021. The odds ratio and 95% confidence interval were used to estimate the strength of the associations.
RESULTS
Ten articles including 2599 cases and 2845 controls were enrolled in our research after strict literature screening. Highly significant associations between the IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all five gene models (allelic, dominant, recessive, homozygous, and heterozygous models), and subgroup analysis based on ethnicity revealed that these associations existed not only in the Asian population but also in the Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated with the IL-17F rs763780 polymorphism, and a slightly lower colorectal cancer susceptibility for the Caucasian population was discovered in the recessive and homozygous models of this mutation.
CONCLUSION
The IL-17A rs2275913 polymorphism may be an independent risk factor contributing to colorectal cancer susceptibility, while the IL-17F rs763780 polymorphism may decrease susceptibility to colorectal cancer. Future studies with large-scale samples are warranted to identify these associations.
Topics: Humans; Case-Control Studies; Colorectal Neoplasms; Genetic Predisposition to Disease; Interleukin-17; Polymorphism, Single Nucleotide
PubMed: 35410225
DOI: 10.1186/s12957-022-02586-2 -
Medicina (Kaunas, Lithuania) Apr 2021Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of and and the risk of oral cancer (OC).
METHODS
PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg's and Egger's tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results.
RESULTS
Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 ( = 0.78), 0.86 ( = 0.55), 0.78 ( = 0.37), 0.83 ( = 0.45), and 1.10 ( = 0.34), respectively. The pooled ORs polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 ( = 0.87), 1.17 ( = 0.82), 1.44 ( = 0.38), 1.28 ( = 0.61), and 0.96 ( = 0.93), respectively. There was no association between polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association.
CONCLUSIONS
The meta-analysis confirmed that there was no association between the polymorphisms of and and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of and the risk OC.
Topics: Genetic Predisposition to Disease; Humans; Interleukin-6; Interleukin-8; Mouth Neoplasms; Polymorphism, Genetic; Risk Factors
PubMed: 33922260
DOI: 10.3390/medicina57050405 -
BMC Endocrine Disorders Feb 2018Many studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERβ gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.
METHODS
PubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association.
RESULTS
Overall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERβ RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations.
CONCLUSION
Each ERα and ERβ gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.
Topics: Bone Density; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genetic Predisposition to Disease; Genotype; Humans; Osteoporosis, Postmenopausal; Polymorphism, Genetic
PubMed: 29458346
DOI: 10.1186/s12902-018-0230-x -
BioMed Research International 2016. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms with diabetic retinopathy (DR) susceptibility reported conflicting results. A systematic... (Meta-Analysis)
Meta-Analysis Review
. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms with diabetic retinopathy (DR) susceptibility reported conflicting results. A systematic meta-analysis was undertaken to clarify this topic. . A systematic search of electronic databases (PubMed, EMBASE, and CNKI) was carried out until March 31, 2016. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. . A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (649 cases and 707 controls). Pooled ORs showed a significant association between FokI polymorphism and DR risk in all the four genetic models (OR = 1.612 (1.354~1.921), 1.988 (1.481~2.668), 1.889 (1.424~2.505), and 2.674 (1.493~4.790) in allelic, dominant, recessive, and additive models, resp., < 0.01), but not for TaqI or BsmI polymorphism ( > 0.05). Similar results were found in the subgroup analysis. Sensitivity analysis indicated that the results were relatively stable and reliable. Results of Begg's and Egger's tests suggested a lack of publication bias. . Our meta-analysis demonstrated that DR was significantly associated with VDR gene FokI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be done to confirm the findings.
Topics: Diabetic Retinopathy; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptors, Calcitriol
PubMed: 27891515
DOI: 10.1155/2016/5305282