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Spine Jun 2017A systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
STUDY DESIGN
A systematic review and meta-analysis.
OBJECTIVE
The aim of this study was to assess and synthesize the current evidence on the association between the rs1256120 single nucleotide polymorphism (SNP) of the estrogen receptor beta gene (ESR2) and adolescent idiopathic scoliosis (AIS).
SUMMARY OF BACKGROUND DATA
Hormonal disturbance has been postulated as a potential etiological factor in the development of AIS. As estrogen receptors are important mediators of estrogen response, mutations in these genes, including rs1256120 of ESR2, have been chosen as susceptibility candidates for AIS predisposition. The association of rs1256120 with AIS has been investigated in several recent studies, but showed conflicting evidence. We conducted a systematic review to evaluate the strength of this body of evidence and quantitative synthesis to examine sources of heterogeneity.
METHODS
This study conformed to PRISMA guidelines. Using a sensitive search strategy, PubMed (MEDLINE), EMBASE, and HuGE Literature Finder databases were searched to identify relevant studies for inclusion in the systematic review and meta-analysis. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. The inverse variance model was used to calculate summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the allelic (C vs. T) and genotypic comparisons. Planned subgroup and sensitivity analyses were performed.
RESULTS
Three studies were included for systematic review and meta-analysis (n = 1264 AIS cases and n=1020 controls). A null relationship was found between rs1256120 and AIS (allelic OR = 1.20, 95% CI: 0.81-1.78, P = 0.36, I = 84.9%), with the first reported association likely to be false-positive and contributing substantially to heterogeneity.
CONCLUSION
Findings from the systematic review and meta-analysis suggest that rs1256120 of ESR2 is unlikely to be a predisposing or disease-modifying genetic risk factor for AIS.
LEVEL OF EVIDENCE
2.
Topics: Adolescent; Alleles; Estrogen Receptor beta; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Scoliosis
PubMed: 27755497
DOI: 10.1097/BRS.0000000000001932 -
Frontiers in Oncology 2023Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs...
BACKGROUND
Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk.
METHODS
PubMed, Embase, and Web of Science were searched for articles including "SNP" and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals () were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The -score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type.
RESULTS
A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model.
CONCLUSIONS
According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.
PubMed: 36874118
DOI: 10.3389/fonc.2023.1094309 -
Genetics in Medicine : Official Journal... Oct 2010Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related phenotype of ischemic stroke are inconclusive. We performed a meta-analysis of published studies investigating the association between ischemic stroke and two nonsynonymous PON1 polymorphisms, rs662 (p.Q192R) and rs854560 (p.L55M) in humans.
METHODS
We searched multiple electronic databases through June 30, 2009 for eligible studies. In main analyses, we calculated allele-based odds ratios with random effects models. In secondary analyses, we examined dominant and recessive genetic models as well, and performed subgroup and sensitivity analyses.
RESULTS
Regarding rs662, we identified 22 eligible studies (total of 7384 cases/11,074 controls), yielding a summary odds ratio of 1.10 per G allele (95% confidence interval, 1.04-1.17) with no evidence of between-study heterogeneity. For rs854560, 16 eligible studies (total of 5518 cases/8951 controls) yielded a summary odds ratio of 0.97 per T allele (95% confidence interval, 0.90-1.04), again with no evidence of between-study heterogeneity. For both polymorphisms, analyses with dominant and recessive genetic models yielded the same inferences as allele-based comparisons. Subgroup and sensitivity analyses showed similar results.
CONCLUSION
In agreement with observations in coronary artery disease, PON1 rs662 appears to be associated with a small increase in the risk of ischemic stroke.
Topics: Alleles; Aryldialkylphosphatase; Brain Ischemia; Confidence Intervals; Coronary Disease; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Phenotype; Polymorphism, Genetic; Risk Factors; Stroke
PubMed: 20856122
DOI: 10.1097/GIM.0b013e3181ee81c6 -
Medical Science Monitor : International... Jun 2016BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions.
Topics: Alleles; Case-Control Studies; Chromosomes, Human, Pair 8; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Polymorphism, Single Nucleotide; Risk Factors; Thyroid Neoplasms
PubMed: 27251952
DOI: 10.12659/msm.896507 -
EBioMedicine Nov 2016Increasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Increasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC.
METHODS
Firstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review.
FINDINGS
20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14-1.61; dominant model: OR 1.36, 95%CI 1.15-1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38-3.00; dominant model: OR 1.20, 95%CI 1.01-1.42; recessive model: OR 1.96, 95%CI 1.33-2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61-0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.48, 95%CI 0.36-0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.49, 95%CI 0.37-0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation.
CONCLUSION
This meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.
Topics: Alleles; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk; Stomach Neoplasms; DNA Methyltransferase 3B
PubMed: 27789275
DOI: 10.1016/j.ebiom.2016.10.028 -
PloS One 2014Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln) and treatment outcomes of patients with advanced gastric cancer.
METHODOLOGY/PRINCIPAL FINDINGS
We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR) for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated by pooled Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs). We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet.
CONCLUSIONS/SIGNIFICANCE
There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification.
Topics: Adult; Aged; Alleles; Antineoplastic Agents; Cisplatin; DNA-Binding Proteins; Databases, Bibliographic; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Stomach Neoplasms; Survival Analysis; Treatment Outcome; X-ray Repair Cross Complementing Protein 1
PubMed: 24465544
DOI: 10.1371/journal.pone.0085357 -
BMC Infectious Diseases Jun 2016The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in... (Review)
Review
BACKGROUND
The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population.
METHODS
An existing DNA repository of 200 each of patients and controls was typed for HLA-DQ by PCR-SSP. Next generation sequencing-based typing for HLA-A, HLA-B and HLA-DRB1 alleles was done in a subset of 280 samples. Association tests were performed on 28,489 genotyped and imputed SNPs spanning a region of 1.4 Mb across the HLA genes. To compare our results with similar studies, we carried out a systematic review to document all HLA associations reported to-date for cutaneous and muco-cutaneous leishmaniasis.
RESULTS
DRB1*04 DQB1*02 (P = 0.03; Pc = 0.09), DRB1*07 DQB1*02 (P = 0.03; Pc = 0.09) haplotypes were absent in patients. B*07 (P = 0.007; Pc = 0.13; OR = 0.36; 95 % CI = 0.17-0.77) allele and DRB1*15 DQB1*06 (P = 0.00; Pc < 0.01; OR = 0.3; 95 % CI = 0.2-.0.6) haplotype were over represented in controls and DRB1*15 (P = 0.002; Pc = 0.01) allele was over represented in patients. Two SNPs (rs281864595/rs1050517) in the antigen recognition region of HLA-B, comprised a haplotype more frequent in controls (P = 0.04). The alleles identified by the systematic review to predispose or to protect from cutaneous/mucocutaneous leishmaniasis remained highly heterogeneous in different populations studied.
CONCLUSIONS
Our preliminary findings suggest a role for some class I and class II HLA genes in determining predisposition to LCL in this population which should be corroborated with further studies. The systematic review reiterates this need, as the purported susceptibility or protection gained by certain HLA alleles or haplotypes has rarely been independently verified.
Topics: Adolescent; Adult; Alleles; Asian People; Case-Control Studies; Child; Child, Preschool; Ethnicity; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; HLA-A Antigens; HLA-B Antigens; HLA-DQ beta-Chains; HLA-DRB1 Chains; Haplotypes; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Leishmaniasis, Cutaneous; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sri Lanka; Young Adult
PubMed: 27301744
DOI: 10.1186/s12879-016-1626-8 -
Journal of Research in Health Sciences Oct 2017The Arg213His (rs9282861) polymorphism of Sulfotransferase Family 1A Member 1 (SULT1A1) gene has been associated with risk of breast cancer in some epidemiological... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Arg213His (rs9282861) polymorphism of Sulfotransferase Family 1A Member 1 (SULT1A1) gene has been associated with risk of breast cancer in some epidemiological studies. Therefore, this systematic review and meta-analysis was conducted to evaluate the association of SULT1A1 Arg213His (rs9282861) polymorphism with susceptibility to breast cancer.
STUDY DESIGN
A systematic review and meta-analysis.
METHODS
A comprehensive literature search for eligible studies was conducted in PubMed, Elsevier, Science Direct, Scopus and Google Scholar databases up to Oct 5, 2017. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to evaluate the strength of the association using fixed effects models and random effects models.
RESULTS
Twenty relevant case-control studies involving 11077 cases and 14798 controls were included in this meta-analysis. Overall, there was a significant association between the SULT1A1 Arg213His (rs9282861) polymorphism and risk of breast cancer in the allele mode (A vs. G: OR=1.117, 95% CI: 1.011, 1.233, P=0.029) and the homozygote model (AA vs. GG: OR=1.288, 95% CI: 1.036, 1.601, P=0.022). Subgroup analysis based on ethnicity suggested SULT1A1 Arg213His (rs9282861) polymorphism had a subtly increased breast cancer risk among Asian population, but not Caucasians. Further, subgroup analyses, significant associations were observed in hospital-based group, RFLP-PCR group, and high-quality studies subgroups.
CONCLUSIONS
SULT1A1 Arg213His (rs9282861) polymorphism might be associated with breast cancer risk, especially among Asian population. Moreover, the SULT1A1 Arg213His polymorphism is of high clinical relevance by ethnicity and would be a useful marker to identify patients who are at higher risk for breast cancer.
Topics: Alleles; Arylsulfotransferase; Asian People; Breast Neoplasms; Female; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; White People
PubMed: 29233949
DOI: No ID Found -
Transplant Immunology Jan 2013We investigated the contribution of polymorphisms in cytokine genes (TNFa-308, IL10-1082 and -592, TGFb1-c10 and c25, and IFNg+874) on the risk of graft rejection in... (Meta-Analysis)
Meta-Analysis Review
We investigated the contribution of polymorphisms in cytokine genes (TNFa-308, IL10-1082 and -592, TGFb1-c10 and c25, and IFNg+874) on the risk of graft rejection in liver transplantation. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. In total, 12 studies were eligible and included in the study. Data extraction and assessments for risk of bias were independently performed by two reviewers. Data for allele frequencies, allelic, and genotypic effects were pooled. Heterogeneity and publication bias were assessed. Pooled minor allele frequencies for TNFa-308, IL10-1082, TGFb1-c10, TGFb1-c25, IFNg+874, and IL10-592 were 0.140 (95% CI: 0.083, 0.198), 0.432 (95% CI: 0.392, 0.472), 0.387 (95% CI: 0.307, 0.467), 0.090 (95% CI: 0.056, 0.123), 0.460 (95% CI: 0.392, 0.528), and 0.224 (95% CI: 0.178, 0.269), respectively. OnlyTNFa-308 and IL10-1082 polymorphisms were significantly associated with graft rejection. Patients who carried minor homozygous genotypes for these two polymorphisms were at 3.5 and 1.69 times higher risk of graft rejections than patients who carried major homozygous genotypes. The estimated lambdas were 0.41 and 0.47, suggesting an additive mode of effect was most likely. However, we could not detect the associations of TGFb1at c10 and c25, INFg+874, and IL10-592 polymorphisms and graft rejection. In summary, our systematic review has demonstrated that TNFa-308 and IL10-1082 are potential risk factors of poor outcomes in liver transplantation. Future updated meta-analysis studies to confirm the power of these genotypes in association with allograft rejection are needed.
Topics: Cytokines; Gene Frequency; Genotype; Graft Rejection; Humans; Liver Transplantation; Polymorphism, Genetic; Postoperative Complications; Risk Factors
PubMed: 23104141
DOI: 10.1016/j.trim.2012.10.003 -
Thrombosis and Haemostasis Jul 2012
Meta-Analysis Review
Topics: Alleles; Aryl Hydrocarbon Hydroxylases; Clopidogrel; Cytochrome P-450 CYP2C19; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Hemorrhage; Humans; Polymorphism, Genetic; Risk; Thrombosis; Ticlopidine
PubMed: 22552318
DOI: 10.1160/TH12-02-0095