Genetic Comparison Models Research Articles

Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and pancreatic cancer

BackgroundPrior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer.MethodsThe comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).ResultsThe analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70–0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58–0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52–0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57–0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05).ConclusionsThe XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain.

Interleukin-10 -1082 G/A polymorphism and its association with early or severe presentation of coronary artery disease: A systematic review and meta-analysis.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies. Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test. A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95% CI 1.02, 1.50), p=0.03; OR 1.32 (95% CI 1.03, 1.69), p=0.03 and OR 1.18 (95% CI 1.02, 1.36), p=0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p=NS). Sensitivity analysis showed consistent results. IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.

MTHFR C667T polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus: An updated meta-analysis

Abstract Background Numerous studies indicated that there exists a relationship between methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and diabetic nephropathy (DN) susceptibility; nonetheless, available proof reported from individual studies has not been consistent, so we performed an updated meta-analysis to evaluate the relationship between MTHFR C667T variant and DN. Materials and methods Relevant studies published before February 2022 were searched from the electronic databases PubMed, Embase, Scopus, Chinese Biology Medicine and the Chinese National Knowledge Infrastructure. The strength of the association was examined by odds ratio (OR) with 95% confidence interval (CI). Results The findings illustrated that there was a significant relationship between the polymorphism of C677T and DN compared with that to DM controls in allele (OR = 1.59, 95% CI = 1.39–1.82), dominant (OR = 1.76, 95% CI = 1.47–2.11) and recessive (OR = 1.85, 95% CI = 1.56–2.20) models in all populations. Moreover, as compared with the healthy controls, a significant relationship between C677T and DN was found in three genetic comparison models (allele: OR = 1.81, 95% CI = 1.43–2.29; dominant: OR = 2.09, 95% CI = 1.54–2.85; recessive: OR = 2.02, 95% CI = 1.51–2.70). Furthermore, stratifying data by race, diabetes duration and whether in Hardy–Weinberg equilibrium revealed substantially augmented vulnerability to DN in all subgroups. Conclusion The current meta-analysis highlighted conclusive results for the robust association between C677T polymorphisms and DN susceptibility.

Lack of association between C282Y and H63D polymorphisms in the hemochromatosis gene and risk of multiple sclerosis: A meta-analysis.

Increasing evidence supports the potential role of iron metabolism in multiple sclerosis (MS). Previous studies examining the association between polymorphisms of the hemochromatosis gene (HFE) and susceptibility to MS have yielded inconsistent results. In the present study, a meta-analysis of 7 studies was performed conducted in populations of Caucasian origin using the Comprehensive Meta-analysis 3.0 software. The strength of association between the C282Y and H63D polymorphisms in HFE and MS risk was estimated by odds ratios with 95% confidence intervals. Cochran's Q statistic and I2 tests were applied to quantify heterogeneity between studies. An Egger's test was used to estimate publication bias. The C282Y and H63D polymorphisms had no significant association with increased MS risk (all P≥0.05) in the following genetic comparison models: Dominant model (YY + CY vs. CC or DD + HD vs. HH) and allele contrast (Y vs. C or D vs. H). No apparent publication bias or significant heterogeneity was found between studies. These results suggest that the HFE polymorphisms C282Y and H63D are not associated with susceptibility to MS in populations of Caucasian origin. Further studies should be performed in a larger series of MS patients to evaluate the contribution of HFE and other genetic variants associated with iron regulation in the development and progression of MS.

Interleukin 6 –174 G/C polymorphism: its relation to coronary artery disease and circulating IL-6 levels – a systematic review and meta-analysis

Abstract Introduction Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 –174 G/C, rs1800795) have been found to be independently associated with coronary artery disease (CAD). However, the association status of this polymorphism with CAD remains unclear. Purpose We conducted a systematic review and updated meta-analysis to comprehensively ascertain the association status of IL6 –174 G/C with CAD and its effect on the levels of circulating IL-6 in humans. Methods Comprehensive online search was undertaken to find relevant case-control/cohort studies investigating the association of IL6 –174 G/C with CAD. The association status of –174 G/C with CAD amongst pooled sample as well as separately amongst different ancestral populations was assessed. Association of –174 G/C with circulating IL-6 levels was also assessed amongst pooled sample as well as separately for CAD cases and CAD-free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled by Mantel-Haenszel fixed-effects models. Results Quantitative synthesis for assessing the role of this polymorphic variant in CAD was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases / 32,053 controls). The pooled association of –174 G/C with CAD was found to be statistically significant through dominant (OR= 1.15, 95% CI= 1.05–1.25, p=0.002) as well as allelic genetic model comparisons (OR= 1.13, 95% CI= 1.06–1.21, p=0.0003). Asian and Asian-Indian ancestral subgroups showed significant association with CAD in both genetic model comparisons (OR range= 1.29 to 1.53, p value range ≤0.02). Other ancestral subgroups did not show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the “C” allele carriers in the pooled sample (Standard mean difference, SMD= 0.31, 95% CI= 0.01–0.22 pg/ml, p=0.009) as well as the CAD-free control subgroup (SMD= 0.10, 95% CI= 0.02–0.17 pg/ml, p=0.009). CAD case subgroup did not show any significant association (p=0.12). Conclusions The present systematic review and meta-analysis confirms an association between IL6 –174 G/C polymorphism residing in the IL6 gene and CAD, especially amongst Asian and Asian-Indian ancestral groups. Upregulation of plasma IL-6 levels in the “C” allele carriers seem to be at least partly responsible for the observed association. Further investigations with large structured case-control studies amongst these ancestral groups are warranted. Funding Acknowledgement Type of funding sources: None.

Lack of Impact of the A1298C MTHFR on the Risk of Childhood Acute Lymphoblastic Leukemia: Evidence from a Meta-analysis.

To clarify the effect of the A1298Cvariant of methylenetetrahydrofolate reductase (MTHFR) gene on the risk of acute lymphoblastic leukemia (ALL), an updated meta-analysis was performed. Electronic literature search was carried out in PubMed to collect relevant articles. Pooled odds ratios (OR) and stratification analysis were achieved under different genetic comparison models, age and ethnicity. A total of 46 articles including 7020 cases and 12,114 controls were enrolled. Overall, no significant association was observed for the MTHFR A1298C variant on the risk of ALL in any genetic model test, when all the studies pooled together (OR ~ 1 0.91; p > 0.05). In subgroup analyses stratified by age and ethnicity, the MTHFR A1298C reduce the risk of ALL in adult under allele contrast (OR = 0.88; [0.72; 1.09], p = 0.23) mainly in Caucasian populations. The present meta-analysis provides evidence that the A1298C variant of MTHFR gene is unlikely to be a major risk gene for childhood ALL.

CTLA-4 +49 A/G Polymorphism and the Risk of Lung Cancer: a Meta-analysis.

Background and objectiveLung cancer is one of the malignant tumors. Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells. Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 adenine (A)/guanine (G) polymorphism and susceptibility of lung cancer, but the results remain controversial. Thus, we performed this meta-analysis to derive a more comprehensive estimation of the relationship.MethodsAll articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the PubMed, EMBASE databases published up to June 29, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Publication bias of relevant studies was examined via Begg's test and funnel plots.ResultsThe meta-analysis included 8 case-control studies covering 4, 430 lung cancer patients and 5, 198 healthy controls from September 2008 to April 2020. The overall eligible data indicated that CTLA-4 +49A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models (dominant model: OR=1.037, 95%CI: 0.925-1.161; recessive model: OR=0.968, 95%CI: 0.888-1.055; allele model: OR=0.992, 95%CI: 0.933-1.054; homozygous model: OR=0.980, 95%CI: 0.857-1.121; heterozygous model: OR=1.023, 95%CI: 0.906-1.154). In further stratified analyses, CTLA-4 +49A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models (dominant model: OR=1.404, 95%CI: 1.074-1.836; allele model: OR=1.273, 95%CI: 1.034-1.565; homozygous model: OR=1.553, 95%CI: 1.044-2.310; heterozygous model: OR=1.308, 95%CI: 1.062-1.611).ConclusionCTLA-4 +49A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.

Methylenetetrahydrofolate reductase genetic polymorphism and the risk of diabetic nephropathy in type 2 diabetic patients.

Background:As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility.Materials and method:Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs).Results:The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (OR = 1.64, 95% CI = 1.34–2.00, P < .001), dominant (OR = 1.85, 95% CI = 1.40–2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27–2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82–3.57, P < .001), and recessive (OR = 1.89, 95% CI = 1.50–2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58–2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73–3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50–5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96–2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations.Conclusion:The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.

Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis

Mannose-binding lectin (MBL), an essential innate immune molecule, enhances the opsonization process and activates the complement system. Genetic variations at the promoter and coding region of the MBL-2 gene have been associated with susceptibility to systemic lupus erythematosus (SLE); however, reports remained inconsistent. The present study performs a meta-analysis of published peer-reviewed articles to draw a definitive conclusion. Published peer-reviewed articles on the association of MBL-2 gene polymorphisms and SLE were screened on various databases such as PubMed (Medline), ScienceDirect, and Google Scholar. A total of 23 eligible articles were included in the present study, comprising 3074 SLE patients and 3985 controls. Genotype and/or allele data for MBL-2 polymorphisms (A > B, A > C, A > D, A > O, Y > X and H > L) were extracted and analyzed by Comprehensive Meta-Analysis software (CMA V3.1). The overall analysis revealed a significant association of MBL-2 (A > O) polymorphism with a predisposition to SLE in allele contrast (p = 0.000; OR = 1.261), homozygous (p = 0.005; OR = 1.482), heterozygous (p = 0.004; OR = 1.247), dominant (p = 0.000; OR = 1.303) and recessive (p = 0.025; OR = 1.356) genetic comparison model. Similar results were also observed in the comparison of allele and the dominant genetic model of MBL-2 (A > B) polymorphism in overall (allele: p = 0.000, OR = 1.46, dominant: p = 0.001, OR = 1.31) and in the Asian cohorts (allele: p = 0.007, OR = 1.43, dominant: p = 0.008, OR = 1.32). Interestingly, MBL-2 (Y-221X) polymorphism exhibited protection against the development of SLE in heterozygous (p = 0.005, OR = 0.619) and dominant genetic comparison (p = 0.01, OR = 0.672) models. MBL-2 variants (A > O and A > B) are associated with predisposition to SLE. Conversely, promoter polymorphism (Y-221X) offers protection against SLE development.

Meta-analysis of NFKB1-94 ATTG Ins/Del Polymorphism and Risk of Breast Cancer.

Breast cancer (BC) accounts for one of the most prevalent malignancies in the world. Inflammatory molecules modulate tumor microenvironment in BC that promotes tumor growth and metastasis. NF-κB (a transcription factor) that regulates multiple immune functions and acts as a crucial mediator of inflammatory responses. The present study is aimed to quantitatively summarize the relation of NFKB1-94 ATTG (I, insertion/D, deletion) variant and risk of BC. Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D polymorphism, and BC patients. Web of Science, PubMed and Embase databases were used to retrieve relevant data. OR and 95% confidence interval of pooled studies were analyzed by using the MetaGenyo web tool. This study revealed a high heterogeneity. In all three genetic comparison models, the NFKB1-94 ATTG I/D variant is not related to the risk of BC. Further, no publication bias on the connection between NFKB1-94 ATTG I/D variant and risk of BC was observed. To summarize, our meta-analysis demonstrates that the NFKB1-94 ATTG I/D polymorphism is not a major risk factor for BC.

Assessment of the relationship between methylenetetrahydrofolate reductase polymorphism and acute lymphoblastic leukemia: Evidence from an updated meta-analysis.

The methylenetetrahydrofolate reductase gene C677T polymorphism is closely related to the acute lymphoblastic leukemia. Several case-control studies have investigated this association; however, no conclusions could be drawn. A comprehensive updated meta-analysis is established to explain these contradictions and clarify the overall impact of this variant on the susceptibility to acute lymphoblastic leukemia. Electronic searches were conducted to select published studies prior to June 2018. Pooled odds ratios and stratification analysis were performed under different genetic comparison models, age, and ethnicity. Totally, 66 case-control studies including 9619 acute lymphoblastic leukemia cases and 17,396 controls were selected. Our analyses showed that methylenetetrahydrofolate reductase C677T polymorphism was protective mainly in Asian and European countries, under all genetic models and regardless of age, but leukemogenic in mixed population. Thus, C677T polymorphism may be a promising acute lymphoblastic leukemia biomarker, but they should be interpreted with caution considering other factors such as folic acid intake, gene-gene and gene-environment interactions.

Association of β-fibrinogen polymorphisms and venous thromboembolism risk: A PRISMA-compliant meta-analysis.

Background:Venous thromboembolism (VTE) is a multifactorial disease in which genetic and acquired risk factors may contribute to disease pathogenesis. Several studies have demonstrated that β-fibrinogen (FGB) polymorphisms are associated with the risk of VTE. However, the results of these studies were not totally consistent. In this paper, we performed a meta-analysis to further investigate the relationship between FGB polymorphisms and susceptibility to VTE.Methods:To identify studies pertinent to the focused question, the following databases were systematically searched: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. The strength of correlations was evaluated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity, type of disorders, and source of control were also performed.Results:Overall, A total of 18 relevant case-control studies met the inclusion criteria and were incorporated in this meta-analysis, involving 3033 VTE cases and 4547 healthy controls. FGB -455G>A polymorphism and -148C>T polymorphism were not significantly associated with susceptibility to VTE in overall populations. However, results of stratified analysis demonstrated that among Caucasian population, the -455G>A mutation was negatively associated with the risk of VTE under all genetic comparison models (A:G OR = 0.80 95% CI = 0.70–0.91; GA + AA:GG OR = 0.80 95% CI = 0.68–0.93; GA:GG OR = 0.84 95% CI = 0.71–0.98; AA:GG + GA OR = 0.61 95% CI = 0.43–0.87; AA:GG OR = 0.57 95% CI = 0.40–0.82), which indicates FGB -455G>A polymorphism may be a protective factor for VTE. There was no correlation between -148C>T polymorphism and susceptibility to VTE in all subgroup analyses.Conclusion:FGB -455G>A polymorphism was associated with a decreased risk of VTE among the Caucasian population.

Association between FSAP 1601G>A polymorphism and venous thromboembolism risk: A meta-analysis.

Previous several studies have shown that factor VII-activating protease (FSAP) gene 1601G>A polymorphism is related to the occurrence of venous thromboembolism, but the results are inconsistent and controversial. Therefore, we conducted a meta-analysis to explore the association between FSAP 1601G>A polymorphism and venous thromboembolism susceptibility. We managed a systematic literature search through Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases to collect research data related to FSAP gene 1601G>A polymorphism and susceptibility to venous thromboembolism published before May 2019. Data analysis was performed through Revman 5.3 and Stata 12.0 software, the pooled odd ratios and 95% confidence intervals were calculated. Additionally, the sensitivity analysis and publication bias assessment were also performed. A total of seven case-control studies were included and evaluated, including 2411 venous thromboembolism cases and 2850 controls. The meta-analysis results revealed that the FSAP 1601G>A mutation is associated with venous thromboembolism risk, and statistically significance was observed under three genetic comparison models (A: G, odds ratio: 1.33, 95% confidence interval: 1.07-1.66; GA: GG, odds ratio: 1.34, 95% confidence interval: 1.06-1.68; and GA + AA: GG, odds ratio: 1.33, 95% confidence interval: 1.06-1.66). This study demonstrated that the FSAP 1601G>A polymorphism may be associated with venous thromboembolism susceptibility.

Association of Matrix Metalloproteinase 9 (MMP-9) Polymorphisms with Asthma Risk: A Meta-Analysis.

Published data on the association between MMP-9 polymorphisms (−1562 C > T, rs3918242; Gln279Arg, rs17576 Arg668Gln, rs17577) and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger's test were inspected for indication of publication bias. Seven studies with 1592 asthma patients and 1987 controls were finally identified. Overall, we found no significant association between −1562 C > T, rs3918242 polymorphism, and asthma susceptibility in any of the genetic model comparisons. After categorizing studies into different subgroups on the basis of ethnicity and age, there is still no significant association. For the Gln279Arg, rs17576 polymorphism, there seems to be a significant association in the allelic genetic model in regard to the P value (OR = 1.11, 95% CI = 1.00–1.22, I 2 = 0%, P (Z)=0.044); however, the value of lower 95% CI is 1.0. For the Arg668Gln, rs17577 polymorphism, a high significant association was observed in the dominant model comparison (OR = 1.65, 95% CI = 1.28–2.11, I 2 = 22.50%, P (Z)=0), recessive model comparison (OR = 2.40, 95% CI = 1.23–4.72, I 2 = 0%, P (Z)=0.011), homozygote genotype comparison (OR = 2.69, 95% CI = 1.36–5.33, I 2 = 0%, P (Z)=0.004), and allelic genetic model (OR = 1.59, 95% CI = 1.29–1.97, I 2 = 36.9%, P (Z)=0). Sensitivity analysis demonstrated the stability of our results, and publication bias was not evident. The present meta-analysis suggests that MMP-9 Arg668Gln, rs17577 polymorphism may be the risk factor for asthma susceptibility.

Association between p73 gene G4C14-to-A4T14 polymorphism and risk of lung cancer: A meta-analysis.

To explore the correlation between p73 G4C14-to-A4T14 polymorphism and lung cancer risk. The meta analysis was conducted from October 2017 to March 2018, and comprised studies published till March 27, 2018, that addressed the relationship between the p73 G4C14-to-A4T14 polymorphism and risk of lung cancer, and were available on databases including PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure. Pooled odds ratio with corresponding 95% confidence interval and subgroup analysis between ethnicities were carried out to assess the association between the two parameters using four different models. Stata 12 was used for data analysis. For overall population, there was no significant risk of lung cancer for the polymorphism under allele and dominant genetic models. However, reduced risks were found under homozygous (AT/AT vs GC/GC; p=0.02) and recessive (AT/AT vs GC/AT + GC/GC; p=0.02) comparison models. Subgroup analysis between ethnicities demonstrated reduced risk of lung cancer for the polymorphism under the four genetic comparison models for Asian population, but increased risk for the Caucasian group. AT/AT variant carriers possessed reduced susceptibility of lung cancer in the general population. Ethnic differences for the p73 gene polymorphism played an important role in lung cancer susceptibility.

Association between MCP-1 -2518A>G polymorphism and asthma susceptibility: a meta-analysis.

The published data on the association between MCP-1 -2518A>G polymorphism and asthma susceptibility are inconclusive. Therefore, we performed a meta-analysis to estimate the impact of MCP-1 -2518A>G polymorphism on asthma susceptibility. PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were used to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the estimates of overall effect, and funnel plots and Egger's test were used to assess publication bias. Eight publications with 1562 asthma patients and 1574 controls were finally identified. Overall, we found no significant association between MCP-1 -2518A>G polymorphism and asthma susceptibility in any of the genetic model comparisons. After stratified analysis by ethnicity, the results showed that a significant association with asthma risk was found in Caucasians in all the genetic models. However, a protective association was found in Africans under the dominant model. The present meta-analysis suggested that the MCP-1 -2518 A>G polymorphism is a risk factor for asthma in the Caucasian population, nevertheless it has a protective effect in the African population.

Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and susceptibility to preterm birth: A case-control study and meta-analysis

BackgroundPreterm birth is the largest contributor to newborn mortality, morbidity, and hospitalization in the first year of life worldwide. Previous studies have suggested the importance of genetic variation in the angiotensin-converting enzyme gene, including the angiotensin-converting enzyme gene insertion/deletion polymorphism, in association with preterm birth. The angiotensin-converting enzyme is a key component of the renin-angiotensin system that is involved in blood pressure homeostasis during pregnancy and also affects risk factors of preterm birth, including the regulation of fibrinolytic system, uteroplacental circulation, vascularization of the placenta, and inflammation. ObjectiveThe results of previous studies investigating the association between the insertion/deletion polymorphism and susceptibility to preterm birth have been inconsistent, therefore, we have performed a case-control study and conducted a meta-analysis of related studies to clarify this association. Study designIn a case-control genetic association study, performed on 217 women with a history of preterm birth and 158 women who experienced full-term pregnancy, the significances of associations between allelic and genotype frequencies and preterm birth were determined using Chi-square tests. Following the case-control study, PubMed, Scopus, Google Scholar, and HugeNavigator databases were systematically searched to identify relevant studies. Altogether, four eligible studies involving 369 cases and 559 controls were included in the meta-analysis. The strength of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism for preterm birth was estimated by odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs), using a fixed-effects model (Mantel-Haenszel method). ResultsIn our case-control study we did not detect a significant association of angiotensin-converting enzyme insertion/deletion alleles and genotypes with preterm birth. The results of the meta-analysis showed a significant association between the angiotensin-converting enzyme gene insertion/deletion and the risk of preterm birth under allelic, dominant, and recessive comparison genetic models (D vs. I: OR = 1.35, 95% CI = 1.11–1.65, p = 0.0033; DD + ID vs. II: OR = 1.52, 95% CI = 1.08–2.15, p = 0.0161; DD vs. ID + II: OR = 1.48, 95% CI = 1.07–2.04, p = 0.0184). ConclusionsThe present meta-analysis suggests that the insertion/deletion polymorphism of the angiotensin-converting enzyme gene in mothers might be associated with preterm birth, however, further well-designed large replication studies involving various ethnicities are needed to confirm this association.

Association between VEGF Gene Polymorphisms and the Susceptibility to Lung Cancer: An Updated Meta-Analysis.

Background and Objective The association between vascular endothelial growth factor (VEGF) gene polymorphisms (-2578C/A, +936C/T, and -460C/T) and lung cancer risk has been extensively studied in the last decades, but currently available results remain controversial or ambiguous. Therefore, we conducted a meta-analysis to assess whether the relationship between the VEGF gene and lung cancer susceptibility exists. Methods The meta-analysis was conducted by searching the databases PubMed, Embase, and Web of Science covering all eligible studies published up to October 1, 2017. The pooled odds ratios (ORs) as well as their 95% confidence intervals (CIs) were utilized to evaluate the possible associations. Publication bias of relevant studies was examined via Begg's funnel plots and Egger's regression tests. Results This meta-analysis included 13 published case–control studies covering 4477 patients with lung cancer and 4346 healthy controls, who had been accrued from December 1992 to July 2012. For the overall eligible data collected in our meta-analysis, it indicated that VEGF +936C/T, -460C/T, and -2578C/A polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models. Moreover, VEGF +460T/C polymorphism was found to be significantly associated with susceptibility to lung cancer in these models (allele model: pooled OR = 1.12, 95% CI: 1.00–1.26, P = 0.184; homozygote model: pooled OR = 1.51, 95% CI: 1.12–2.03, P = 0.821), but no significant results were detected in Caucasian populations. Conclusions VEGF +936C/T, -460C/T, and -2578C/A polymorphisms were not associated with the risk of lung cancer. The VEGF +460T/C polymorphism might be a risk factor for lung cancer only in Asian populations.

Collagen IX gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis

BackgroundAn increasing number of studies have investigated associations between collagen IX alpha 2 chain (COL9A2) and collagen IX alpha 3 chain (COL9A3) gene polymorphisms and the risk of lumbar disc degeneration (LDD). However, these studies have yielded contradictory results. The purpose of this meta-analysis is to investigate the association between the collagen IX gene polymorphisms (rs12077871, rs12722877, rs7533552 in COL9A2; rs61734651 in COL9A3) and LDD.MethodsAll relevant articles were collected from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). The last electronic search was performed on September 1, 2017. The allele/genotype frequencies were extracted from each study. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of associations under the five comparison genetic models. Statistical analysis was performed by Review Manager (RevMan) 5.31 software.ResultsThe meta-analysis of 10 case-control studies, including 2102 LDD cases and 2507 controls, indicated that COL9A2 gene (rs12077871, rs12722877, rs7533552) and COL9A3 gene (rs61734651) polymorphisms were not associated with LDD (rs12077871: T vs. C, OR = 1.85, 95% CI = 0.87–3.91, P = 0.11; rs12722877: G vs. C, OR = 0.83, 95% CI = 0.69–1.01, P = 0.06; rs7533552: G vs. A, OR = 1.11, 95% CI = 0.98–1.25, P = 0.09; rs61734651: T vs. C, OR = 1.57, 95% CI = 0.51–4.84, P = 0.43). The Egger text and the Begg funnel plot did not show any evidence of publication bias.Conclusionrs12077871, rs12722877, and rs7533552 variants in COL9A2 and rs61734651 variant in COL9A3 were not significantly associated with a predisposition to LDD. Large-scale and well-designed studies are needed to confirm this conclusion.

Association of IRX3 rs3751723 polymorphism with the risk of overweight and obesity: case-control study and meta-analysis

Association of the iroquois homeobox 3 (IRX3) rs3751723 polymorphism has been shown to increase the risk of obesity, but the data are underreported in the Malaysian population. Therefore, this study sought to investigate this association in the Malaysian population using both a case-control study and a meta-analysis. Genotyping of the IRX3 rs3751723 polymorphism was performed for 1030 age-matched Malaysians using hydrolysis probe. Odds ratios were calculated with 95% confidence intervals. A meta-analysis was conducted using Comprehensive Meta Analysis software Ver. 2.2.064. Our results showed that the variant G/G genotype was significantly associated with a higher risk of obesity in the Malaysian population, especially in individuals who did not intake fast-food. The presence of the variant G allele was linked to overweight susceptibility in Malaysian females, but seemed to be protective against being overweight and obese among current smokers. However, a meta-analysis showed no significant associations between this polymorphism and obesity in all genetic comparison models. In summary, this study established a significant relationship between the IRX3 rs3751723 polymorphism and gender and lifestyle differences with respect to susceptibility of overweight and obesity in the Malaysian population; yet no significant association was found in a meta-analysis. Taken together, these data could be beneficial for informing personal health management decisions and population-based study designs that target overweight susceptibility and obesity.