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.     

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 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.     

Role of Endoglin Insertion and rs1800956 Polymorphisms in Intracranial Aneurysm Susceptibility: A Meta-Analysis

Endoglin is an essential molecule during angiogenesis, vascular development, and integrity. Till now, many studies have investigated the association between endoglin polymorphisms and intracranial aneurysm (IA) risk, with the results remained inconclusive. Therefore, we performed a meta-analysis to summarize the possible association.We searched PubMed and Embase until June 2015 to identify studies addressing the association between endoglin polymorphisms and IA risk. The summary odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated to assess the strength of the association.Eleven studies with a total of 1501 cases and 2012 controls were finally included in this meta-analysis, with 10 studies investigating endoglin 6-bp insertion (6bINS) polymorphism and 4 studies investigating 1800956 polymorphism. No significant association between endoglin 6bINS polymorphism and IA risk was detected in overall estimation (I/I vs wt/I + wt/wt: OR = 1.21, 95% CI = 0.87–1.69) or in the subgroup analysis by ethnicity, control source, or ruptured status. However, we observed an association with borderline significance of 6bINS with IA occurrence (I/I vs wt/I + wt/wt: OR = 1.49, 95% CI = 0.99–2.25, P = 0.058) in studies applying matched controls. Furthermore, we detected a significant association for 6bINS polymorphism of endoglin with increased risk of familial IA (I vs wt, OR = 1.64, 95% CI = 1.10–2.42) but not sporadic IA (I vs wt, OR = 1.09, 95% CI = 0.68–1.45). With regard to rs1800956, our pooled results indicated a significantly decreased IA risk in individuals carrying C allele (C/C vs G/C + G/G: OR = 0.65; 95% CI = 0.45–0.94).This meta-analysis provided no evidence for the association between 6bINS polymorphism with overall IA risk. However, we detected a significant association of 6bINS allele with increased risk of familial IA. Also, we found that rs1800956 was significantly related to IA occurrence. Further, well-designed studies with large sample size are warranted and updated meta-analysis is needed to verify our findings.     

The Catalase C-262T Gene Polymorphism and Cancer Risk: A Systematic Review and Meta-analysis

Many studies suggest that catalase C-262T gene polymorphism is associated with cancer risk, but with inconsistent results. This study aimed to summarize the overall association between catalase C-262T polymorphism and cancer risk. Literature search was performed in PubMed, Embase, and other databases, studies regarding the association between catalase C-262T polymorphism and cancer risk were identified, and data were retrieved and analyzed by using Review Manager 5.0.24 and STATA 12.0. A total of 18 publications with 22 case–control studies, including 9777 cancer patients and 12,223 controls, met the inclusion criteria. Meta-analysis results showed significant association between catalase C-262 T polymorphism and cancer risk (TT vs CT + CC: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03–1.31, P = 0.01). Subgroup analyses stratified by cancer types suggested the catalase C-262T polymorphism was significantly associated with an increased prostate cancer risk (TT vs CT + CC: OR = 1.61, 95% CI = 1.17–2.22, P = 0.004); for subgroup analyses stratified by ethnicity, no associations between this polymorphism and Asians or whites were identified (CT + TT vs CC: OR = 1.11, 95% CI = 0.98–1.26, P = 0.09 for whites; OR = 1.19, 95% CI = 0.78–1.80, P = 0.42 for Asians). In summary, the catalase C-262T polymorphism may be a risk factor for cancer with cancer type-specific effects. Further studies should be performed to confirm these findings.     

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.     

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.     

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61–0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54–0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55–0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff–Bloom–Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.     

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.     

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 polymorphisms in the interleukin-10 gene and susceptibility to human immunodeficiency virus-1 infection: A systematic review and meta-analysis

Background:This study meta-analyzed the literature on possible association of 3 polymorphisms (-592, -1082, -819) in the interleukin-10 (IL-10) gene with susceptibility to human immunodeficiency virus (HIV)-1 infection.Methods:PubMed, EMBASE, MEDLINE and Google Scholar were systematically searched to identify relevant studies in English. Meta-analyses were performed to examine the association of IL-10 polymorphisms -592, -1082, and -819 with susceptibility to HIV-1 infection.Results:A significant association between the -592 polymorphism and susceptibility to HIV-1 infection was found in the total population (recessive model, odds ratios (OR) = 1.44, 95% CI = 1.06–1.96, P = .02; homozygous model, OR = 1.44, 95% CI = 1.02–2.02, P = .04). However, these results were not observed in subgroups based on ethnicity. The -1082 polymorphism was significantly associated with susceptibility to HIV-1 infection in Caucasians (OR = 1.30, 95% CI = 1.05–1.62, P = .02; recessive model, OR = 1.49, 95% CI = 1.09–2.03, P = .01; homozygous model, OR = 1.58, 95% CI = 1.01–2.46, P = .04), but not in Asians or the total population. None of the 5 genetic models suggested a significant association between the -819 polymorphism and HIV-1 infection.Conclusion:The available evidence indicates that the AA genotype of IL-10 -592 may confer increased susceptibility to HIV-1 infection, and that the AA genotype of -1082 may confer increased susceptibility in Caucasians. In contrast, the -819 polymorphism may not be associated with HIV-1 infection risk. These conclusions should be verified in large, well-designed studies.     

Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis

Objective:To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer.Methods:Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots.Results:Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190–1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216–1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172–1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778–0.933, P = .001).Conclusion:The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility.     

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.     

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.     

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.     

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.     

The association between polymorphism of the long noncoding RNA,Plasmacytoma variant translocation 1, and the risk of gastric cancer

Genetic polymorphisms of plasmacytoma variant translocation 1 can affect various tumors including gastro-intestinal, sexual hormone sensitive cancers and lymphoma. Accumulated evidence have shown that plasmacytoma variant translocation 1 acts as an oncogene and tumor suppressor in various cancers. In fact, the rs13255292 and rs2608053 single nucleotide polymorphisms of plasmacytoma variant translocation 1are known to affect lymphoma; however, their effects on gastric cancer are primarily unknown. In this study, we evaluated the association between these plasmacytoma variant translocation 1 polymorphisms and the risk of gastric cancer.In the present study, 462 patients diagnosed with gastric cancer and 377 cancer-free controls were enrolled. The TaqMan genotyping assay was used to analyze the association between rs13255292 and rs2608053 single nucleotide polymorphisms and the risk of gastric cancer.The rs2608053 dominant model (CT + TT) was associated with a decreased risk of gastric cancer in T3 + T4 (odds ratio [OR] = 0.61, confidence interval (CI) = 0.41 – 0.92, P = .019), and stage III Gastric cancer subgroups (OR = 0.59, 95% CI = 0.38 – 0.91, P = .017) compared to the CC genotype. When stratified analysis by sex was carried out, the rs13255292 dominant model (CT + TT) had a significant association with an increased risk of gastric cancer in the female negative lymph node metastasis gastric cancer subgroup, compared to the CC genotype (OR = 1.96, 95% CI = 1.16 – 3.30, P = .012). The recessive model (TT) of rs13255292 was associated with an increased risk of gastric cancer in the male T3 + T4 gastric cancer subgroups compared to the CC + CT genotype (OR = 3.82, 95% CI = 1.02 – 14.33, P = .047). The dominant model (CT + TT) of rs2608053 was related to a decreased risk of gastric cancer in male T3 + T4 (OR = 0.57, 95% CI = 0.33 – 0.98, P = .042) and stage III gastric cancer subgroups (OR = 0.49, 95% CI = 0.27 – 0.89, P = .020) compared to the CC genotype.The rs13255292 and rs2608053 single nucleotide polymorphisms in plasmacytoma variant translocation 1 may contribute to susceptibility of gastric cancer. Further studies with more subjects and different ethnic groups are needed to validate our results.     

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.