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Frontiers in Endocrinology 2022The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity... (Meta-Analysis)
Meta-Analysis
G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis.
BACKGROUND
The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity indexes as well as serum lipid levels have been extensively investigated in various studies, but the results were inconsistent and even contradictory.
METHODS
PubMed, Google Scholar, Embase, Cochrane Library, Web of Science, Wanfang, CNKI and VIP databases were searched for eligible studies. The random-effTPDEects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in obesity indexes and serum lipid levels between the subjects with different genotypes in a dominant model. Heterogeneity among studies was assessed by Cochran's x-based Q-statistic test. Publication bias was identified by using Begg's test.
RESULTS
One hundred and twenty studies (70,317 subjects) and 33 studies (18,353 subjects) were identified in the analyses for the rs1801282 and rs3856806 polymorphisms, respectively. The G allele carriers of the rs1801282 polymorphism had higher levels of body mass index (SMD = 0.08 kg/m, 95% CI = 0.04 to 0.12 kg/m, < 0.001), waist circumference (SMD = 0.12 cm, 95% CI = 0.06 to 0.18 cm, < 0.001) and total cholesterol (SMD = 0.07 mmol/L, 95% CI = 0.02 to 0.11 mmol/L, < 0.01) than the CC homozygotes. The T allele carriers of the rs3856806 polymorphism had lower levels of low-density lipoprotein cholesterol (SMD = -0.09 mmol/L, 95% CI = -0.15 to -0.03 mmol/L, < 0.01) and higher levels of high-density lipoprotein cholesterol (SMD = 0.06 mmol/L, 95% CI = 0.02 to 0.10 mmol/L, < 0.01) than the CC homozygotes.
CONCLUSIONS
The meta-analysis suggests that the G allele of the rs1801282 polymorphism confers an increased risk of obesity and hypercholesterolemia, while the T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia, which can partly explain the associations between these polymorphisms and cardiovascular disease.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier [CRD42022319347].
Topics: Alleles; Cholesterol, HDL; Dyslipidemias; Humans; Hypercholesterolemia; Obesity; PPAR gamma; Polymorphism, Single Nucleotide
PubMed: 35846293
DOI: 10.3389/fendo.2022.919087 -
Tumour Biology : the Journal of the... Feb 2014Epidemiological studies have assessed the association between HIF-1α polymorphisms and cancer risk. However, the results remained conflicting rather than conclusive.... (Meta-Analysis)
Meta-Analysis Review
Epidemiological studies have assessed the association between HIF-1α polymorphisms and cancer risk. However, the results remained conflicting rather than conclusive. Therefore, we performed a systematic review to provide a complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases until July 2013 to identify eligible studies. Data sets (43) from 39 studies with a total of 10,841 cases and 14,682 controls were included. The most commonly investigated polymorphism was C1772T, followed by G1790A, C111A, and rs2057482. Overall, C1772T and G1790A but not rs2057482 were associated with increased risk for cancer. When stratified by cancer type, C1772T was associated with increased risk for cervical cancer (T/T vs. C/T+C/C: OR = 8.80, 95 % CI = 2.30-33.70), prostate cancer (T vs. C: OR = 1.54, 95 % CI = 1.04-2.30), and other cancers (T vs. C: OR = 1.42, 95 % CI = 1.07-1.89), but not oral, breast, colorectal, endometrial, lung, and bladder cancers or renal cell carcinoma. G1790A was associated with marginal but insignificant risk for prostate cancer (A vs. G: OR = 1.46, 95 % CI = 1.00-2.13, P = 0.056) and with increased risk for oral (A vs. G: OR = 9.66, 95 % CI = 1.31-71.15), lung (A vs. G: OR = 2.27, 95 % CI = 1.74-2.96), and other cancers (A vs. G: OR = 2.06, 95 % CI = 1.26-3.37) and renal cell carcinoma (A/A vs. G/A+G/G: OR = 3.05, 95 % CI = 1.36-6.84), but not breast, colorectal, cervical, or bladder cancer. Furthermore, we detected increased cancer risk in haplotypes TA and CA and in those carrying at least one risk allele, and decreased cancer risk in haplotype TG regarding C1772T and G1790A polymorphisms. Further well-designed studies on various cancer types are warranted to verify our findings.
Topics: Alleles; China; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Polymorphism, Genetic; Risk Factors
PubMed: 24046090
DOI: 10.1007/s13277-013-1160-x -
Rheumatology International Feb 2012The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on associations between serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) S/L allele, catechol-O-methltransferase (COMT) val158Met, and serotonin 2A (5-HT2A) receptor 102T/C polymorphisms and fibromyalgia susceptibility as determined using the following: (1) allele contrast, (2) recessive, (3) dominant models, and (4) contrast of homozygotes. We also performed a systematic review with available data of the candidate genes. A total of 21 separate comparisons were considered in this systematic review and meta-analysis. Seventeen candidate genes and over 35 different polymorphisms were identified in studies on fibromyalgia susceptibility. Meta-analysis of the 5-HTTLPR S/L allele and COMT val158Met failed to reveal any association with fibromyalgia. However, meta-analysis of the C allele, CC + CT genotype, and CC versus TT genotype of the 5-HT2A receptor 102T/C polymorphism showed significant association with fibromyalgia. The overall OR of the association between the C allele and fibromyalgia was 1.333 (95% CI = 1.053-1.688, P = 0.017). The ORs for the CC + CT genotype, and CC versus TT genotype showed the same pattern as that observed for the C allele (OR = 1.541, 95% CI = 1.032-2.303, P = 0.035; OR = 1.838, 95% CI = 1.151-2.936, P = 0.011). This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia. In contrast, no association was found between the 5-HTTLPR S/L allele, COMT val158Met, and susceptibility to fibromyalgia.
Topics: Alleles; Catechol O-Methyltransferase; Fibromyalgia; Genes, Dominant; Genes, Recessive; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Neurotransmitter; Serotonin Plasma Membrane Transport Proteins
PubMed: 21120487
DOI: 10.1007/s00296-010-1678-9 -
Jornal Brasileiro de Pneumologia :... 2024To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
CONCLUSIONS
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
Topics: Humans; Alleles; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Pyridines; Indoles; Pyrazoles; Aminophenols; Quinolones; Pyrrolidines; Benzodioxoles
PubMed: 38198345
DOI: 10.36416/1806-3756/e20230187 -
International Journal of Epidemiology Feb 2016Low penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Low penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/].
METHODS
We performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations.
RESULTS
We considered the association with the rs6983267 variant at 8q24 as 'highly credible', reaching genome-wide statistical significance in at least one meta-analysis model. We identified 'less credible' associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations.
CONCLUSIONS
The limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRA gene database provides context for CRA genetic association data and will help inform future research directions.
Topics: Adenoma; Alleles; Arylamine N-Acetyltransferase; Bayes Theorem; Colorectal Neoplasms; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Isoenzymes; Methylenetetrahydrofolate Reductase (NADPH2); NAD(P)H Dehydrogenase (Quinone); Polymorphism, Single Nucleotide; Risk Factors; Tumor Suppressor Protein p53
PubMed: 26451011
DOI: 10.1093/ije/dyv185 -
Human Reproduction Update 2013Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were... (Review)
Review
BACKGROUND
Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
METHODS
Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
RESULTS
Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372.
CONCLUSIONS
In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Topics: Alleles; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Secretion; Polymorphism, Single Nucleotide; Pregnancy; RNA-Binding Proteins; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Risk; Transcription Factor 7-Like 2 Protein; tRNA Methyltransferases
PubMed: 23690305
DOI: 10.1093/humupd/dmt013 -
Immunobiology Jun 2015Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in rheumatoid arthritis (RA). However, published studies demonstrated differences concerning... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in rheumatoid arthritis (RA). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and RA risk.
OBJECTIVE
The aim of the current study was to quantify the magnitude of the association between TaqI, BsmI, and FokI VDR polymorphisms with RA risk.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature were conducted. Analyses were performed in the random effects model by using recessive, dominant, codominant, homozygous, and allele contrast models.
RESULTS
A total of 1703 cases and 2635 controls in 12 case-control studies were included in the meta-analyses. Results indicated a significant association between TaqI polymorphism and RA disease in homozygous, codominant and allele contrast models (P=0.008, P=0.015, P=0.006 and P=0.002, respectively). Association between BsmI polymorphism and RA risk was marginal in the dominant, codominant and allele contrast models (P=0.057, P=0.071, and P=0.069, respectively). Te association between FokI polymorphism and RA risk was significant in the recessive, dominant and allele contrast models (P=0.045, P=0.027, and P=0.013, respectively). Subgroup analysis showed that publication year, ethnicity, age, latitude, and estimated 25(OH)D levels influenced significantly the association between VDR polymorphisms and RA risk.
CONCLUSION
TaqI and FokI VDR polymorphisms contributed significantly to RA risk. Study characteristics influenced the association between VDR polymorphisms and RA disease.
Topics: Alleles; Arthritis, Rheumatoid; Case-Control Studies; Genetic Predisposition to Disease; Genotype; Humans; Odds Ratio; Polymorphism, Genetic; Receptors, Calcitriol
PubMed: 25577294
DOI: 10.1016/j.imbio.2014.12.013 -
Neurology Jul 2013We aimed to examine the association of APOE ε genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to examine the association of APOE ε genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.
METHODS
We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n = 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis.
RESULTS
APOE ε4 carrier status and APOE ε44 genotype were associated with increasing white matter hyperintensity burden (sample size-weighted z score meta-analysis [meta]-p = 0.0034 and 0.0030) and presence of cerebral microbleeds (meta odds ratio [OR] = 1.24, 95% confidence interval [CI] [1.07, 1.43], p = 0.004, and 1.87 [1.26, 2.78], p = 0.002), especially lobar. APOE ε2 carrier status was associated with increasing white matter hyperintensity load (z score meta-p = 0.00053) and risk of brain infarct (meta OR = 1.41[1.09, 1.81], p = 0.008).
CONCLUSIONS
APOE ε4 and APOE ε2 were associated with increasing burden in MRI markers for both hemorrhagic and ischemic CVD. While the association of APOE ε4 with an increased burden of CVD could be partly contributing to the relationship between APOE ε4 and AD, APOE ε2 was associated with MRI markers of CVD in the opposite direction compared to AD.
Topics: Alleles; Apolipoproteins E; Brain; Cerebrovascular Disorders; Genetic Predisposition to Disease; Genotype; Humans; Magnetic Resonance Imaging; Risk
PubMed: 23858411
DOI: 10.1212/WNL.0b013e31829bfda4 -
PloS One 2013Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status.
METHODS
By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China.
RESULTS
At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3-5.5%) and 2.1% (0.1-4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0-21.7%) and 8.0% (4.5-11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3-11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays.
CONCLUSION
The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.
Topics: Alleles; Celiac Disease; China; Databases, Bibliographic; Gene Expression; Gene Frequency; Genetic Heterogeneity; Glutens; HLA-DQ Antigens; HLA-DQ beta-Chains; Haplotypes; Histocompatibility Testing; Humans; Incidence
PubMed: 24324669
DOI: 10.1371/journal.pone.0081151 -
The Journal of Asthma : Official... Dec 2012To determine whether there is an association between the toll-like receptor 4 (TLR4) +896A>G single nucleotide polymorphism and asthma by conducting a systematic review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether there is an association between the toll-like receptor 4 (TLR4) +896A>G single nucleotide polymorphism and asthma by conducting a systematic review and meta-analysis.
METHODS
The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search for relevant studies was performed using PubMed (MEDLINE), Scopus, and HuGE Literature Finder databases with additional consultation of the reference lists of included studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for the allelic comparison (G vs. A) and the genotypic comparison assuming a dominant genetic model (AG + GG vs. AA). I² statistics were calculated to assess the presence of between-study heterogeneity and funnel plots were inspected for indication of publication bias. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates.
RESULTS
Meta-analysis of nine studies consisting of 1838 asthma cases and 1764 controls did not find a significant association between TLR4 +896A>G and asthma (genotypic OR = 1.12, 95% CI: 0.91-1.39, p = .27). Between-study heterogeneity was not detected (I² = 0%) and publication bias was not evident. Sensitivity analysis demonstrated the stability of the null association.
CONCLUSIONS
The meta-analysis findings suggest a lack of direct association between the TLR4 +896A>G polymorphism and asthma, but gene-environment and gene-gene interaction effects and other considerations involving this polymorphism may exist. Therefore, further study is necessary to fully elucidate the role of TLR4 +896A>G in asthma.
Topics: Alleles; Asthma; Gene-Environment Interaction; Genotype; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Toll-Like Receptor 4
PubMed: 23574398
DOI: 10.3109/02770903.2012.738270