Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism and Vesicoureteral Reflux in Children: A Meta-Analysis of 14 Case–Control Studies

Vesicoureteral reflux (VUR) is a common and serious urinary disease in children. It usually causes renal scar, urinary tract infection, and chronic renal failure. Previous studies showed the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism might be associated with VUR; however, the conclusions were inconsistent. Therefore we used the meta-analytic approach to clarify the effect of ACE I/D polymorphism on VUR risk.We systematically searched the PubMed, CNKI, and EMBASE databases to identify all the potentially related studies published up to February 4, 2015. Two reviewers independently selected studies and extracted data. The strength of the association was assessed using odd ratio (OR) with its 95% confidence interval (CI) based on fixed or random effects model. The STATA 12.0 software was used for data analysis.A total of 14 case–control studies involving 1197 VUR patients and 1320 healthy controls met the eligibility criteria. Results of meta-analysis showed significant association between ACE I/D polymorphism and VUR risk (D vs. I: OR = 1.28, 95% CI = 1.06–1.54, P = 0.01; DD vs. II: OR = 1.44, 95% CI = 1.12–1.85, P = 0.01; DD vs. DI + II: OR = 1.49, 95% CI = 1.23–1.79, P < 0.01; DD + DI vs. II: OR = 1.20, 95% CI = 0.84–1.72, P = 0.31). Subgroup analyses revealed varied results. In Turkish people, results of all the genetic models other than DI vs. II showed statistical significance; in Caucasians, DD vs. DI + II showed statistical significance; and in Asians, DI versus II showed statistical significance.Our meta-analysis indicated that the ACE I/D polymorphism might be associated with increased risk of VUR in children. However, due to the limitations, we suggest conducting additional studies with larger sample size and adjustment for various risk factors, in the future for further clarification.     

The Polymorphism of CYP2E1 Rsa I/Pst I Gene and Susceptibility to Respiratory System Cancer: A Systematic Review and Meta-Analysis of 34 Studies

The purpose of this articles is to determine whether the cytochrome P450 2E1 (CYP2E1) Rsa I/Pst I gene polymorphism is correlated with respiratory system cancers.Respiratory system cancers included lung cancer, laryngeal cancer, nasopharyngeal cancer, and cancers of other respiratory organs, which are the most common malignant tumors worldwide; the significant relationship between CYP2E1 Rsa I/Pst I gene polymorphism and some respiratory system cancer have been reported, but results of some other studies are controversial. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association.PubMed, EMBASE, Cochrane Library Databases, China National Knowledge Infrastructure, and Wanfang Database (up to July 20, 2014) were searched for all case–control studies those mainly studied the relationship between CYP2E1 Rsa I/Pst I gene polymorphism and the susceptibility of respiratory system cancer.A total of 332 articles were collected, among which 34 studies that involved 7028 cases and 9822 controls fulfilled the inclusion criteria after being assessed by 2 reviewers. When stratified by cancer site, the C2/C2 polymorphism could increase the risk of nasopharyngeal cancer under the homozygote model (C2C2 vs C1C1: OR = 1.85, 95% CI = 1.20–2.85, P = 0.005) and recessive model (C2C2 vs C1C2/C1C1: OR = 1.89, 95% CI = 1.23–2.89, P = 0.003). Protection effect was found in lung cancer in heterozygote model (C1C2 vs C1C1: OR = 0.82, 95% CI = 0.74–0.91, P < 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.83, 95% CI = 0.76–0.90, P < 0.001), and allele contrast model (C2 vs C1: OR = 0.85, 95% CI = 0.73–1.00, P = 0.045). With regard to ethnicity subgroup analysis, there was significant association in Asian population in heterozygote model (C1C2 vs C1C1: OR = 0.85, 95% CI = 0.78–0.94, P = 0.001), dominant model (C1C2/C2C2 vs C1C1: OR = 0.88, 95% CI = 0.81–0.95, P = 0.001), and recessive model (C2C2 vs C1C2/C1C1: OR = 1.25, 95% CI = 1.01–1.53, P = 0.036).CYP2E1 Rsa I/Pst I gene polymorphism may reduce the risk of respiratory system cancer. Furthermore, significant association was also found in Asian populations.     

Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk

Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis.Case–control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms.We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR = 1.44, 95% CI = 1.04–1.99, P values for heterogeneity test (Q-test) [P_Het] = 0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile + Ile/Ile: OR = 1.41, 95% CI = 1.02–1.95, P_Het = 0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR = 1.16, 95% CI = 1.00–1.36, P_Het = 0.323; Val/Val + Ile/Val vs Ile/Ile: OR = 1.15, 95% CI = 0.99–1.34, P_Het = 0.253).These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations.     

No Association of SERPINE1 ?675 Polymorphism With Sepsis Susceptibility: A Meta-Analysis

The serine protease inhibitor clade E member 1 (SERPINE1) gene has been suggested to exert great influence on the development of sepsis. But there is little overlap in the results of association between SERPINE1 −675 4G/5G polymorphism and sepsis.To get a more precise estimation of this association, we conducted a meta-analysis with a relatively larger sample size including 1806 cases and 2239 controls. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between −675 4G/5G polymorphism and sepsis susceptibility. Subgroup analyses were conducted based on ethnicity and source of controls.The results showed that there was no association of the SERPINE1 polymorphism and sepsis susceptibility (5G5G vs 4G4G: OR = 0.87, CI = 0.75–1.03; 5G5G+4G5G vs 4G4G: OR = 0.93, CI = 0.84–1.02; 5G5G vs 4G4G+4G5G: OR = 0.96, CI = 0.83–1.11; 5G vs 4G: OR = 0.94, CI = 0.86–1.01; 4G5G vs 4G4G: OR = 0.90, CI = 0.80–1.01). Nor did any subgroup analysis indicate a significant association.In conclusion, −675 4G/5G polymorphism in the SERPINE1 gene may not be associated with the risk of sepsis.     

Association Between Three eNOS Polymorphisms and Intracranial Aneurysms Risk: A Meta-Analysis

Endothelial nitric oxide synthase (eNOS) is the catalyst of endothelial nitric oxide (NO) synthesis. Polymorphisms in the eNOS gene may influence the risk of intracranial aneurysm (IA), but the results of existing researches are still inconsistent. Thus, we performed the present meta-analysis to derive a more precise estimation between eNOS polymorphisms (T786C, G894T, 27-bp-variable number of tandem repeat [VNTR]) and IA risk.Case–control studies evaluating the association between the eNOS polymorphisms and IA risk were searched in PubMed, Ovid & Embase, Web of Science, and Chinese Wanfang datasets with the last search up to July 15, 2014. The pooled odds ratios (ORs) for the association between eNOS polymorphisms and IA and their corresponding 95% confidence intervals (CIs) were estimated using the random or fixed-effects model.Finally, 10 studies for T786C polymorphism (1819 cases and 1893 controls), 9 studies for G894T polymorphism (1393 cases and 1508 controls), and 7 studies for 27-bp-VNTR polymorphism (1281 cases and 1406 controls) were included in the meta-analyses. In the overall analysis, no evidence of association between eNOS polymorphisms and susceptibility of IA was found. When subgrouped by race descent, significantly increased risk was detected among Asians for T786C polymorphism (heterozygous comparison of codominant model: OR = 1.294, 95% CI = 1.025–1.634; dominant model: OR = 1.277, 95% CI = 1.019–1.600), but not in Caucasians or the other 2 polymorphisms.Our meta-analysis suggested that T786C polymorphism was associated with increased risk of IA among Asians, whereas G894T and 27-bp-VNTR polymorphisms might have no influence on the susceptibility of IA.     

Lack of association between BDNF rs6265 polymorphism and risk of type 2 diabetes: A protocol for meta-analysis and trial sequential analysis

Background:Brain-derived neurotrophic factor (BDNF) rs6265 polymorphism has been previously suggested to be associated with the susceptibility of type 2 diabetes mellitus (T2DM), but results remained controversial. We aim to provide a more reliable conclusion about the association between BDNF rs6265 polymorphism and T2DM risk by using a meta-analysis.Methods:Electronic databases such as Pubmed, Embase, CNKI, and Wanfang were searched for relevant articles published up to May 06, 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Subgroup analysis was carried out according to source of controls and quality score of included studies. A trial sequential analysis was conducted to reduce the risk of type I error.Results:A total of 8 case-control studies (7 conducted in China) with 1576 T2DM patients and 1866 controls were included. Overall, our results indicated no significant association between BDNF rs6265 polymorphism and T2DM risk with the random-effects model (allele model: pooled OR = 1.14, 95% CI = 0.79–1.65, homozygote model: pooled OR = 1.13, 95% CI = 0.57–2.21, heterozygote model: pooled OR = 1.07, 95% CI = 0.78–1.48, dominant model: pooled OR = 1.14, 95% CI = 0.74–1.75 and recessive model: pooled OR = 1.10, 95% CI = 0.67–1.80). Subgroup analysis by source of controls and quality score also showed no significant association between BDNF rs6265 polymorphism and T2DM risk. Trial sequential analysis results confirmed the null association and further studies were unnecessary.Conclusion:This meta-analysis study indicated that no significant association between BDNF rs6265 polymorphism and T2DM risk.     

Is MDM2 SNP309 Variation a Risk Factor for Head and Neck Carcinoma?: An Updated Meta-Analysis Based on 11,552 Individuals

Murine double minute-2 (MDM2) is a negative regulator of P53, and its T309G polymorphism has been suggested as a risk factor for a variety of cancers. Increasing evidence has shown the association of MDM2 T309G polymorphism with head and neck carcinoma (HNC) risk. However, the results are inconsistent. Thus, we performed a meta-analysis to elucidate the association.The meta-analysis retrieved studies published up to August 2015, and essential information was extracted for analysis. Separate analyses on ethnicity, source of controls, sample size, detection method, and cancer types were also conducted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate the association.Pooled data from 16 case–control studies including 4625 cases and 6927 controls failed to indicate a significant association. However, in the subgroup analysis of sample sizes, an increased risk was observed in the largest sample size group (>1000) under a recessive model (OR = 1.52; 95% CI = 1.08–2.13). Increased risks were also found in the nasopharyngeal cancer in the subgroup analysis of cancer types (GG vs TT: OR = 2.07; 95% CI = 1.38–3.12; dominant model: OR = 1.48; 95% CI = 1.13–1.93; recessive model: OR = 1.76; 95% CI = 1.17–2.65).The results suggest that homozygote GG alleles of MDM2 SNP309 may be a low-penetrant risk factor for HNC, and G allele may confer nasopharyngeal cancer susceptibility.     

The Role of TP53 Gene Codon 72 Polymorphism in Leukemia: A PRISMA-Compliant Systematic Review and Meta-Analysis

The purpose of this meta-analysis was aimed to evaluate the association of tumor protein p53 (TP53) gene codon 72 polymorphism with leukemia susceptibility.We searched PubMed to identify relevant studies, and 16 case-control studies from 14 published articles were identified as eligible studies, including 2062 leukemia patients and 5826 controls. After extracting data, odds ratio (OR) with the corresponding 95% confidence interval (95%CI) was applied to assess the association between TP53 codon 72 polymorphism and leukemia susceptibility. The meta-analysis was performed with the Comprehensive Meta-Analysis software, version 2.2.Overall, no significant association between TP53 codon 72 polymorphism and leukemia susceptibility was found in this meta-analysis (Pro vs Arg: OR = 1.05, 95%CI = 0.90–1.21; Pro/Pro vs Arg/Arg: OR = 1.13, 95%CI = 0.84–1.52; Arg/Pro vs Arg/Arg: OR = 0.94, 95%CI = 0.76–1.15; [Pro/Pro + Arg/Pro] vs Arg/Arg: OR = 0.99, 95%CI = 0.80–1.21; Pro/Pro vs [Arg/Arg + Arg/Pro]: OR = 1.19, 95%CI = 0.93–1.51). Similar results were also found in subgroup analysis by ethnicity, source of controls, and types of leukemia (either acute myeloid leukemia or acute lymphocytic leukemia).Our meta-analysis demonstrates that TP53 codon 72 polymorphism may not be a risk factor for acute leukemia; however, due to the limitations of this study, it should be verified in future studies.     

Association Between 3 IL-10 Gene Polymorphisms and Cardiovascular Disease Risk: Systematic Review With Meta-Analysis and Trial Sequential Analysis

Previous studies have yielded controversial results related to the contribution of interleukin 10 (IL-10) gene polymorphisms (IL-10 -592C/A, IL-10 -1082G/A, and IL-10 -819C/T) in the progression of cardiovascular disease (CVD). Thus, we performed a meta-analysis to summarize this situation.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library with the last search up to July 7, 2015. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis was conducted for all significant findings. Genotype-based mRNA expression analysis was also performed using data from 270 individuals with different ethnicities.Finally, 19 studies for IL-10 -592C/A polymorphism (7284 cases and 7469 controls), 21 studies for IL-10 -1082G/A polymorphism (8263 cases and 5765 controls), and 12 studies for IL-10 -819C/T polymorphism (4502 cases and 3190 controls) were included in the meta-analyses. With respect to IL-10 -819C/T polymorphism, statistically significant decreased CVD risk was found when all studies were pooled into the meta-analysis (T vs C: OR = 0.91, 95% CI = 0.84–0.98; TT + TC vs CC: OR = 0.90, 95% CI = 0.81–1.00). Subgroup analyses stratified by disease subtype suggested the -819C/T polymorphism was significantly associated with a decreased CAD risk (T vs C: OR = 0.90, 95% CI = 0.83–0.97; TT vs CC: OR = 0.81, 95% CI = 0.66–1.00; TT vs TC + CC: OR = 0.82, 95% CI = 0.69–0.98; TT + TC vs CC: OR = 0.89, 95% CI = 0.80–0.99), which was noteworthy finding as evaluated by FPRP. However, with regard to IL-10 -592C/A and IL-10 -1082G/A polymorphisms, no significant association with CVD risk was observed in the overall and subgroup analyses.In conventional meta-analyses, the results suggested that IL-10 -819C/T polymorphism was associated with decreased risk of CVD, especially CAD outcome, whereas IL-10 -592C/A and IL-10 -1082G/A polymorphisms might have no influence on the susceptibility of CVD. However, trial sequential analysis does not allow us to draw any solid conclusion for the association between IL-10 -592C/A or IL-10 -1082G/A polymorphism and CVD risk. Further large and well-designed studies are still needed.     

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study

The aim of this study was to investigate the association between 2 polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 and the risk of papillary thyroid carcinoma (PTC).A case-control study of 618 PTC patients and 562 controls was conducted. The rs10877887 polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism and the rs13293512 polymorphism was genotyped by using a TaqMan Genotyping Assay. The results were confirmed by DNA sequencing.The rs10877887 polymorphism had reduced risks of PTC in heterozygous comparison, dominant model, and overdominant model (TC vs TT: adjusted odds ratio [OR] = 0.73, 95% confidence interval [95% CI] = 0.58–0.94, P = 0.01; TC/CC vs TT: adjusted OR = 0.79, 95% CI = 0.63–1.00, P = 0.047; TC vs TT/CC: adjusted OR = 0.73, 95% CI = 0.57–0.92, P = 0.007, respectively). Stratified analyses showed that PTC patients carrying the rs10877887 CC genotype were more likely to have multiple tumors (adjusted OR = 1.71, 95% CI = 1.03–2.86, P = 0.04), and PTC patients carrying the rs13293512 TC + CC or CC were more likely to develop N0 status (TC/CC vs TT: adjusted OR = 0.64, 95% CI = 0.43–0.94, P = 0.02; CC vs TC/TT: adjusted OR = 0.50, 95% CI = 0.33–0.77, P = 0.001, respectively).Our study suggests that the rs10877887 polymorphism may be associated with the risk of PTC and the rs13293512 polymorphism may correlate to lymph node metastasis in PTC.     

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I² index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I² = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I² = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I² = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I² = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I² = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.     

Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case–Control Studies

Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association.Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs).Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52).The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.     

Mitogen-Activated Protein Kinase Kinase 4 Gene Polymorphism and Cancer Risk

A number of epidemiological studies have assessed the association of −1304T > G polymorphism in the MKK4 gene and risk of cancer, but the results lack of statistical power due to the limited subjects used in these studies. This study was devised to identify the genetic effects of the −1304T > G polymorphism on cancer risk in a large meta-analysis.Eligible studies were identified by searching both Chinese and English databases. General as well as subgroup analyses were performed for 8 independent case–control publications with a total of 4623 cases and 5256 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association.Overall, this meta-analysis showed that the association between the −1304T > G polymorphism and cancer risk was statistically significant (GG vs TT: OR = 0.63, 95% CI, 0.52–0.75; GG + TG vs TT: OR = 0.85, 95% CI, 0.79–0.91; GG vs TG + TT: OR = 0.67, 95% CI, 0.56–0.80; G vs T: OR = 0.82, 95% CI, 0.77–0.88; TG vs TT: OR = 0.86, 95% CI, 0.79–0.93).Our meta-analysis reveals that the presence of the −1304T > G polymorphism is likely to decrease risk of cancer. Future larger studies are necessary to validate the current finding.     

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis: An Update Meta-Analysis

The association between vitamin D receptor (VDR) FokI polymorphism and tuberculosis (TB) risk remains a matter of debate. Potential selection bias exists in most studies using HIV-positive TB patients.An update meta-analysis was carried out to derive a more reliable assessment of the association between FokI polymorphisms and TB risk, especially in HIV-negative TB patients. All major databases from inception to June 2015 were searched for all publications that studied the association between FokI polymorphism and TB risk. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated according to the frequencies of genotypes.In total, 32 studies with 4894 cases and 5319 controls were included in this meta-analysis. In the overall analysis, the estimated OR was 1.34 (95% CI=1.091–1.646, P = 0.005) in the best genetic model (recessive model, ff vs fF+FF) with moderate heterogeneity (I² = 32.2%, P = 0.043). In the subgroup analysis stratified by HIV status, significant associations were found only in the HIV-negative TB group (OR = 1.60, 95% CI = 1.180–2.077, P = 0.002; I² = 29.5%, and P = 0.141 for heterogeneity). In the subgroup analysis stratified by ethnicity, significant associations were found in the Asian group (OR = 1.65, 95% CI = 1.205–2.261, P = 0.002; I² = 43.9%, and P = 0.024 for heterogeneity), but not in the Caucasian group (OR = 1.09, 95% CI = 0.762–1.547, P = 0.649; I² = 0.0%, and P = 0.740 for heterogeneity) and African group (OR = 0.99, 95% CI = 0.726–1.341, P = 0.934; I² = 43.9%, and P = 0.024 for heterogeneity).This meta-analysis confirms that VDR FokI polymorphism contributes to the risk of TB, especially in HIV-negative TB patients and in the Asian group. Further studies are required to clarify the role of the FokI polymorphism in HIV-positive TB and in other ethnic groups.     

Growth arrest-specific 5 (GAS5) insertion/deletion polymorphism and cancer susceptibility in Asian populations: A meta-analysis

Background:Previous studies have reported the association of an insertion/deletion (Ins/Del) polymorphism (rs145204276 AGGCA/-) in the promoter region of growth arrest-specific 5 (GAS5) with the risk of cancer, such as breast cancer, gastric cancer, and hepatocellular carcinoma. However, the results are still controversial. We aimed to clarify the association of GAS5 rs145204276 polymorphism with cancer risk by meta-analysis.Methods:PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and Cochrane Library were searched for studies concerning GAS5 and cancer published up to November 25, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate cancer risk.Results:A total of 12 case–control studies with 8729 cases and 10,807 controls were included in this meta-analysis. We found that the GAS5 rs145204276 polymorphism was not significantly associated with cancer risk (Del vs Ins: OR = 0.96, 95% CI: 0.81–1.13; Del/Del vs Ins/Ins: OR = 1.00, 95% CI: 0.70–1.43; Ins/Del vs Ins/Ins: OR = 0.92, 95% CI: 0.78–1.08; Ins/Del and Del/Del vs Ins/Ins: OR = 0.93, 95% CI: 0.76–1.13; Del/Del vs Ins/Del and Ins/Ins: OR = 1.04, 95% CI: 0.78–1.38). In the stratified analyses, significant effects on gastric cancer were found (Del vs Ins: OR = 0.79, 95% CI: 0.72–0.86; Del/Del vs Ins/Ins: OR = 0.65, 95% CI: 0.52–0.82; Ins/Del vs Ins/Ins: OR = 0.76, 95% CI: 0.68–0.86; Ins/Del + Del/Del vs Ins/Ins: OR = 0.74, 95% CI: 0.66–0.83; Del/Del vs Ins/Ins + Ins/Del: OR = 0.74, 95% CI: 0.59–0.91).Conclusion:Our meta-analysis showed that GAS5 rs145204276 polymorphisms were not related to overall cancer risk. However, the GAS5 rs145204276 polymorphism may be a protective factor for gastric cancer in the stratification analyses.     

Association Between IL-4 Polymorphisms and Risk of Liver Disease: An Updated Meta-Analysis

Interleukin-4 (IL-4) polymorphisms have been reported to influence an individual''s susceptibility to liver disease as it is a central anti-inflammatory Th2 cytokine; however, these results remain controversial.A comprehensive meta-analysis of the relevant literature was thus performed to better estimate the relationship between IL-4 polymorphisms and liver disease.Systematic searches of various databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) for studies published before July 5, 2015 were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the association. Subgroup analyses, meta-regression, Galbraith plots, and sensitivity analyses were also performed.A total of 16 case–control studies, of which 15 involved the -590C/T polymorphism and 3 involved the -33T/C polymorphism, were included in the study. With respect to the -590C/T polymorphism, a significantly increased risk of liver diseases was found in the overall population (TT + CT vs CC: OR = 1.25, 95% CI = 1.06–1.49, P = 0.009 and CT vs CC: OR = 1.22, 95% CI = 1.00–1.48, P = 0.048) and the Asian population (TT + CT vs CC: OR = 1.28, 95% CI = 1.04–1.57, P = 0.020). Further subgroup analyses also showed significant associations between the -590C > T polymorphism and the risk of hepatitis C infection and hepatocellular carcinoma. However, no association was found between the -33T/C polymorphism and risk of liver diseases in all comparison models.This meta-analysis suggested that the IL-4 -590C > T polymorphism is associated with an increased risk of hepatitis C infection and hepatocellular carcinoma, especially among the Asian population.     

Analysis of MTR and MTRR Polymorphisms for Neural Tube Defects Risk Association

Neural tube defects (NTDs) are the most common congenital defects of the central nervous system among neonates and the folate status during pregnancy was considered as the most important etiopathogenesis of NTDs. Besides, methionine synthase (MTR) gene and methionine synthase reductase (MTRR) gene were folate metabolism involved genes and had been investigated in several previous studies with inconsistent results. Hence, we aimed to explore the association of 4 selected single-nucleotide polymorphisms (SNPs) on MTRR/MTR gene and the susceptibility of NTDs in a Chinese population.Seven SNPs were selected from HapMap databases with Haploview 4.2 software. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to genotype the polymorphisms from blood samples of 165 NTDs patients and 280 healthy controls. The correlation between these SNPs and NTDs risk was tested by Student t test and Chi-square test by STATA 11.0 software. Furthermore, we performed a meta-analysis of relevant studies to investigate the association between the SNPs MTRR 66A>G and MTR 2756A>G and the susceptibility of NTDs.An increased risk of NTDs was verified to be significantly associated with MTRR 66A>G (G allele vs. A allele: OR = 1.36 (1.03–1.80), P = 0.028; GG + AG vs. AA: OR = 1.60 (1.05–2.43), P = 0.027) and MTR 2756A>G (G allele vs. A allele: OR = 1.45 (1.06–1.98), P = 0.021; GG + AG vs. AA: OR = 1.51 (1.02–2.23), P = 0.038) in our study. However, the other SNPs in our analysis showed no significant association with NTDs risk (all P > 0.05). Furthermore, the result of the meta-analysis supported the association between MTRR 66A>G and NTDs risk (G allele vs. A allele: OR = 1.32, 95% CI = 1.09–1.61, GG + GA vs. AA: OR = 1.49, 95% CI = 1.06–2.09, GG vs. AA: OR = 1.61, 95% CI = 1.04–2.49).Our study confirmed that the MTRR 66A>G and MTR 2756A>G were significantly associated with the increased NTDs risk in a Chinese population. The further meta-analysis enhance that MTRR 66A>G was connected with the susceptibility of NTDs widely. Further investigations based on more detailed stratification were recommended.     

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk

Background:Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.Methods:Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).Results:Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).Conclusion:The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.     

The Transforming Growth Factor-β1 (TGF-β1) Gene Polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and Susceptibility to Postmenopausal Osteoporosis: A Meta-Analysis

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-β1 gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-β1 T869C and TGF-β1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-β1 T869C and TGF-β1 T29C polymorphisms and PMOP (TGF-β1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-β1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-β1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03–1.75, P = 0.028); however, there was no significant association between TGF-β1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-β1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR = 1.37, 95% CI = 1.07–1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16–2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-β1 T869C and TGF-β1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.