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1.
Introduction
Previous studies suggested lipoprotein lipase (LPL) Ser447Ter and Asn291Ser polymorphisms were associated with the risk of ischemic heart disease, however, their effects on ischemic stroke were controversial. A meta-analysis was performed to assess the associations between these two LPL polymorphisms and the risk of ischemic stroke.Methods
The electronic databases PubMed and Embase were used to identify relevant studies by two interviews independently. The pooled odds ratios (ORs) and weighted mean differences (WMD) with 95% confidence interval (CI) were estimated for the risk of ischemic stroke and the plasma lipids in various Ser447Ter genotypes respectively. A fixed or random effect model was selected for pooling data based on homogeneity test.Results
13 studies including 4,681 ischemic stroke cases and 8,516 controls were involved in this meta-analysis. Overall, LPL Ter447 variant was associated with a significantly reduced risk for ischemic stroke (OR = 0.79, 95% CI: 0.68-0.93) both in Caucasian (OR = 0.87, 95% CI: 0.77-0.97) and East-Asian (OR = 0.65, 95% CI: 0.43-0.99), whereas no significant association of Ser291 variant was observed (OR = 1.25, 95% CI: 0.96-1.63). The Ser447Ter polymorphism may be more important in association with the decreased risk of atherosclerotic stroke (OR = 0.44, 95% CI: 0.32-0.62) which derived from significantly increased high density lipoprotein cholesterol, decreased triglyceride and total cholesterol in Ter447 carriers compared with non-carriers.Conclusions
This meta-analysis indicated that LPL Ser447Ter polymorphism was associated with a significant reduction in the risk of ischemic stroke, especially atherosclerotic stroke subtype in both Caucasian and East-Asian. 相似文献2.
Introduction
The ABCB1 C3435T polymorphism limits oral bioavailability of clopidogrel and may influence prognosis of patients treated with clopidogrel. Several studies have examined the association between the C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients, but the results were inconsistent. To assess the role of the C3435T polymorphism in the impact on clinical outcomes, a meta-analysis was conducted.Methods
6 studies with 10,153 subjects were included in this meta-analysis. Fixed- or random-effects model was chosen according to heterogeneity. Publication bias was evaluated by fail-safe numbers.Results
The association of the C3435T polymorphism with risk of overall recurrent ischemic events in clopidogrel treated patients was not statistically significant for all genetic models (OR = 1.13, 95%CI: 0.78-1.64, P = 0.51; OR = 1.15, 95%CI: 0.99-1.33, P = 0.07; OR = 1.19, 95%CI: 0.81-1.76, P = 0.37). Significant association was identified between the C3435T polymorphism and risk of short-term recurrent ischemic events (OR = 1.55, 95% CI: 1.09-2.20, P = 0.01; OR = 1.41, 95% CI: 1.06-1.87, P = 0.02; OR = 1.77, 95% CI: 1.19-2.63, P = 0.005). No statistically significant association between the C3435T polymorphism and stent thrombosis (OR = 0.79, 95% CI: 0.47-1.32, P = 0.37) or bleeding (OR = 0.98, 95% CI: 0.79-1.21, P = 0.82) was identified. The results may be affected by publication bias.Conclusions
This meta-analysis failed to show an association between the ABCB1 C3435T polymorphism and risk of overall recurrent ischemic events, stent thrombosis or bleeding in clopidogrel treated patients. However, the association between TT homozygotes of the C3435T polymorphism and risk of short-term recurrent ischemic events may exist, but needs more studies to confirm. 相似文献3.
G Lian Y Yan L Jianxiong X Juanjuan C Qing W Guangliang S Li 《Thrombosis research》2012,130(3):e95-e102
Background
In 2009, a GWAS has confirmed that rs11833579 and rs12425791 near the NINJ2 gene could increase the stroke and ischemic stroke (IS) risk. Recently, several studies have been implemented to assess the relationship between the two SNPs and ischemic stroke risk in Asian. However, the results were poorly consistent. To study the association between the both polymorphisms and the risk of ischemic stroke, we performed a meta-analysis.Methods
We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of association. The heterogeneity was checked by Q test and the inconsistency index (I2). Begg's test and Egger's test were used to assess the possible publication bias.Results
Our study included 6 articles, contained 9 independent case-control studies, involved a total of 9,142 cases and 10,652 controls about rs11833579, 10,165 cases and 11,592 controls about rs12425791. There was a significant association between rs12425791 and IS risk with dominant genetic model (OR = 1.087, 95%CI = 1.021-1.158, I2 = 34.6%, P = 0.152), but not with recessive genetic model and allele A vs. allele G. For rs11833579, we failed to verify it relate with IS risk under allele A vs. allele G, dominant and recessive genetic model.Conclusions
This meta-analysis suggest that rs12425791 is relative to ischemic stroke risk under dominant model in Asian population, but not for rs11833579. 相似文献4.
Introduction
Factor XIII (FXIII) is a key regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ischemic stroke (IS) has been investigated in a few studies with contradictory results. In spite of their fundamental difference in pathogenesis and hemostatic pathomechanism, only four small studies investigated the effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic IS (AIS) separately from cardioembolic IS. Gender specific effect of the polymorphism on the risk of AIS has not been explored. In the present study we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of AIS on a large patient population.Materials and methods
A population control group of 1,146 randomly selected individuals, 496 patients surviving AIS and their age and sex-matched controls selected from the population control group were included in the study. FXIII-A Val34Leu genotype was determined on DNA samples, obtained from peripheral blood leukocytes, by fluorescence resonance energy transfer detection using melting curve analysis.Results
Neither sex nor age affected the distribution of FXIII-A Val34Leu genotypes in population control group. No association was revealed between the risk of AIS and FXIII-A Leu34 carriership and homozygous or heterozygous presentation of Leu34 allele in either gender.Conclusion
FXIII-A Val34Leu polymorphism fails to influence the risk of AIS. 相似文献5.
Introduction
Growing studies have revealed the underlying association between eNOS 894 G/T (rs1799983) polymorphism and coronary heart disease (CHD) among Asia population. Results from these studies remained conflicting. We conducted this meta-analysis to estimate the overall CHD risk of eNOS 894 G/T polymorphism regarding Asia population.Materials and methods
Up to October 2011, databases including PubMed, Embase and CNKI (China National Knowledge Infrastructure) were searched to access the relevant genetic association studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for eNOS 894 G/T polymorphism and CHD risk were estimated using fixed or random-effects models when appropriate.Results
18 case-control studies with 2,994 cases and 3,130 controls were available for this study, including 13 studies of East-Asia descendents, 5 studies of Non East-Asian descendents. The mean T allele frequency was 0.111 in the East-Asia population and 0.147 in the Non East-Asia population, respectively. The summary OR for CHD associated with the T allele was 1.52 (95% confidence intervals (95%CI), 1.37-1.69) by random effects model. Similarly, significantly increased risks were observed in the East-Asia population (OR = 1.54; 95%CI = 1.35-1.76) and in the Non East-Asia population (OR = 1.48; 95%CI = 1.24-1.77), respectively.Conclusions
This meta-analysis indicated that eNOS 894 G/T polymorphism may play an important role in CHD development among Asia population. 相似文献6.
Lian Gu Wenhui Liu Yan Yan Li Su Guangliang Wu Baoyun Liang Jinjing Tan Guihua Huang 《Thrombosis research》2014
Background
Ischemic stroke (IS) and coronary heart disease (CHD) are two vascular disorders that are a common cause of death worldwide. Several studies have assessed the association of the β-fibrinogen-455G/A (FGB-455G/A) polymorphism and risk of IS and CHD, but the results are still inconsistent. Our study aimed to investigate whether the FGB-455G/A polymorphism was associated with susceptibility to IS and CHD by using meta-analysis.Methods
Relevant studies were identified from PubMed, Embase and four Chinese database up to July 2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was calculated to estimate the strength of the genetic association. Cumulative meta-analysis was performed to assess the tendency of pooled OR over time.Results
45 studies based on a total of 7238 cases and 7395 controls were included in our meta-analysis. The results indicated that the FGB-455G/A polymorphism is associated with the risk of IS when compared with the dominant model (OR = 1.518, 95%CI = 1.279-1.802 for AA + GA vs. GG). In the subgroup analysis by ethnicity, significantly elevated risks were associated with the A allele in Asians (OR = 1.700, 95%CI = 1.417-2.040), but not in Caucasians (OR = 0.942, 95%CI = 0.813-1.091). Both the hypertension and non-hypertension subgroups reached significant results, but no significance was found when stratified according to sex or subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated with CHD (OR = 1.802, 95%CI = 1.445-2.246).Conclusion
Our meta-analysis suggests that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD. 相似文献7.
Introduction
Endothelial nitric oxide synthase (eNOS) 894 G > T polymorphism may influence the risk of thrombotic disease, but data from published studies with low statistical power are inconclusive. To investigate the association between the gene polymorphism and thrombotic disease, a meta-analysis was performed.Materials and Methods
Case–control studies evaluating the association between the eNOS G894T polymorphism, Glu298Asp and thrombotic disease were searched in PubMed, OVID, Web of Science, Google Scholar and China Biology Medicine disc (CBM). Data were available for 4742 cases and 4066 controls from 17 studies.Results
In all, although there was a significant association between G894T and thrombotic disease (G/T + T/T vs. G/G: OR = 1.364, 95%CI = 1.126-1.652, P = 0.001; T/T vs. G/T + G/G: OR = 1.861, 95%CI = 1.207-2.870, P = 0.005; TT vs. GG: OR = 1.938, 95%CI = 1.244-3.021, P = 0.003; G/T vs. G/G: OR = 1.225, 95%CI = 1.022-1.469, P = 0.028), there was significant heterogeneity among studies (P* < 0.001). In subgroup analysis, there was significant association with no heterogeneity in venous thrombosis (G/T + T/T vs. G/G: OR = 1.409, 95%CI = 1.135-1.750, P = 0.002, P* = 0.508; T/T vs. G/G: OR = 1.640, 95%CI = 1.011-2.660, P = 0.045, P* = 0.333; G/T vs. G/G: OR = 1.357, 95%CI = 1.082-1.701, P = 0.008, P* = 0.595) and in Asian population (G/T + T/T vs. G/G: OR = 1.722, 95%CI = 1.443-2.055, P < 0.001, P* = 0.541; T/T vs. G/T + G/G: OR = 2.357, 95%CI = 1.389-4.000, P = 0.001, P* = 0.908; T/T vs. G/G: OR = 2.813, 95%CI = 1.645-4.810, P < 0.001, P* = 0.969; G/T vs. G/G: OR = 1.645, 95%CI = 1.370-1.975, P < 0.001, P* = 0.489).Conclusions
Findings of this meta-analysis demonstrated that eNOS G894T polymorphism may be a risk factor for venous thrombosis, and in Asia the polymorphism may increase the risk of developing thrombotic disease. 相似文献8.
Dragoni F Chiarotti F Rosano G Simioni P Tormene D Mazzucconi MG Cafolla A Avvisati G 《Thrombosis research》2011,127(2):85-90
Introduction
Despite extensive clinical and laboratory investigations, the etiology of ischemic stroke remains unknown in approximately one third of patients.Materials and Methods
Thirty-four consecutive patients less than 40 years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented ischemic stroke underwent, one year after the acute event, laboratory evaluation of antithrombin, protein C, free and total protein S, activated protein C resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR) were also evaluated and compared to the results obtained in 120 normal controls.Results
Antithrombin and protein C levels resulted normal in all cases. One patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had activated protein C resistance. Homocysteine levels above 15 μmol/L were found in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of 120 (1.66%) controls (OR = 95.31; 95% C.I.: 18.22-667.81). The multivariate analysis selected that the presence of APA was significantly associated with an increased risk of stroke (OR = 156.60; 95% C.I.: 25.99-943.47) in this cohort of patients. The combination between APA and cardiovascular risk factors determined a risk of 29-fold (OR = 29.31; 95% CI: 3.28-261.69).Discussion
Our data suggest that the presence of APA is associated with an increased risk of idiopathic ischemic stroke in young patients. Furthermore, also the combination of APA and cardiovascular risk factors is significantly associated with development of idiopathic ischemic stroke. 相似文献9.
Zhou J Huang Y Huang RS Wang F Xu L Le Y Yang X Xu W Huang X Lian J Duan S 《Thrombosis research》2012,130(4):602-606
Introduction
Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.Methods
We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.Results
Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p = 0.04; OR = 1.45, 95% CI = 1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p = 0.04; OR = 1.83, 95% CI = 1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR = 1.08, 95% CI = 1.05 - 1.11) in both Europeans and South Asians including Han Chinese.Conclusions
Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect. 相似文献10.
Nan Li 《Brain research bulletin》2010,81(1):38-42
Background
The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese.Method
A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed.Results
The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p = 0.001, p = 0.003 and p = 0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR = 1.603; 95%CI = 1.032-2.489; p = 0.036 for the CC genotype of the PDE4D (83T/C) and OR = 1.913; 95%CI = 1.621-2.375; p = 0.034 for the TT genotype of the IL-1 (−889C/T), respectively.Conclusions
the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese. 相似文献11.
Constantine N. Antonopoulos George S. SfyroerasJohn D. Kakisis Konstantinos G. MoulakakisChristos D. Liapis 《Thrombosis research》2014
Introduction
Soluble P selectin (sPsel), a member of the selectin family of cell adhesion receptors, has been proposed as a key molecule in hemostasis and thrombosis mediating platelet rolling, generating procoagulant microparticles and enhancing fibrin deposition. The aim of this study was to examine the role of sPsel in the diagnosis of venous thromboembolism (VTE).Materials and Methods
We performed a systematic review and we used meta-analysis to synthesize data from published studies reporting sPsel levels in patients with i) VTE (deep venous thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated among patients and controls. Diagnostic performance of sPsel was tested with pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver operator characteristic (SROC) curve.Results
Eleven studies, comprising of 586 VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly increased after VTE (OR = 2.89, 95%CI = 2.31-3.61, p < 0.001), or DVT only (OR = 2.64, 95%CI = 1.95-3.56, p < 0.001). Subgroup analysis evidenced that sPsel was also increased after VTE when evaluating only studies with patients that had no prior medical history (OR = 2.88, 95%CI = 1.98-4.19, p < 0.001). Exclusion of studies including patients with solid organ tumor, HIV or lupus anticoagulants positive patients did not alter findings. Pooled sensitivity and specificity of sPsel was 0.57 (95%CI = 0.30-082, p < 0.001) and 0.73 (95%CI = 0.51-0.90, p < 0.001), respectively and DOR was 4.31 (95%CI = 2.22-8.37, p < 0.01). SROC curve yielded in significant accuracy of sPsel performance (AUC = 0.74, p = 0.05).Conclusions
The sPsel was significantly elevated in patients with DVT, both uncomplicated and complicated with PE and presented with high levels of diagnostic performance. sPsel is a plasma biomarker that may help in the diagnosis of VTE. 相似文献12.
Objective
Many studies have suggested that adiponectin gene might be involved in the development of coronary artery disease (CAD). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to assess the associations of + 45T/G, + 276G/T and − 11377C/G polymorphisms in adiponectin gene with CAD susceptibility.Methods
Published literature from PubMed and EMBASE databases were searched. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using fixed- or random-effects model.Results
Sixteen studies (4394 cases / 8187 controls) for + 45T/G polymorphism, fifteen studies (3569 cases / 7463 controls) for + 276G/T polymorphism, and thirteen studies (3531 cases / 7072 controls) for − 11377C/G polymorphism were included in the meta-analysis. The overall results showed that there was a statistically significant association between − 11377C/G polymorphism and CAD (G vs. C: OR = 1.15, 95%CI 1.07-1.24).Similar results were observed among European (G vs. C: OR = 1.11, 95%CI 1.02-1.20) and East Asian populations (G vs. C: OR = 1.27, 95%CI 1.11-1.45). However, no significant association was found for + 45T/G or + 276G/T polymorphism with CAD susceptibility.Conclusions
The meta-analysis indicated the significant association of − 11377C/G polymorphism, but not + 45T/G or + 276G/T polymorphism, with CAD susceptibility. However, large-scale studies with the consideration of gene-gene and gene-environment interactions should be conducted to investigate the associations in future. 相似文献13.
Ernest K. Amankwah Christie M. Atchison Shilpa Arlikar Irmel Ayala Laurie Barrett Brian R. Branchford Michael Streiff Clifford Takemoto Neil A. Goldenberg 《Thrombosis research》2014
Objective
To determine hospital-associated venous thromboembolism (HA-VTE) risk factors in critically ill neonates.Methods
We conducted a case-control study in the neonatal intensive care unit (NICU) of All Children’s Hospital Johns Hopkins Medicine (St. Petersburg, FL), from January 1, 2006 - April 10, 2013. We identified HA-VTE cases using electronic health record. Four NICU controls were randomly selected for each HA-VTE case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate regression analyses.Results
Twenty-three HA-VTE cases and 92 controls were included. The annual HA-VTE incidence was approximately 1.4 HA-VTE cases per 1,000 NICU admissions. In univariate analyses, mechanical ventilation (OR = 7.27, 95%CI = 2.02-26.17, P = 0.002), central venous catheter (CVC; OR = 52.95, 95%CI = 6.80-412.71, P < 0.001), infection (OR = 7.24, 95%CI = 2.66-19.72, P < 0.001), major surgery (OR = 5.60, 95%CI = 1.82-17.22, P = 0.003) and length of stay ≥ 15 days (OR = 6.67, 95%CI = 1.85-23.99, P = 0.004) were associated with HA-VTE. Only CVC (OR = 29.04, 95%CI = 3.18-265.26, P = 0.003) remained an independent risk factor in the multivariate analysis. Based on this result, the estimated risk of HA-VTE in NICU patients with a CVC was 0.9%.Conclusion
This study identifies CVC as an independent risk factor for HA-VTE in critically ill neonates. However, the level of risk associated with CVC is below the conventional threshold for primary anticoagulation thromboprophylaxis. Larger studies are needed to substantiate these findings and identify novel putative risk factors to further distinguish NICU patients at highest HA-VTE risk. 相似文献14.
LL Gong JH Peng FF Han J Zhu LH Fang YH Wang GH Du HY Wang LH Liu 《Thrombosis research》2012,130(3):e43-e51
Introduction
To investigate whether t-PA Alu repeat insertion/deletion (I/D) and PAI-1 4 G/5 G genetic variations are associated with the risk of MI.Methods
We conducted a meta-analysis to assess the association between the t-PA I/D and PAI-1 4 G/5 G polymorphisms and risk of MI. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African), gender and age. Forty one eligible studies including 12,461 cases and 14,993 controls were identified to evaluate the impact of PAI-1 4 G/5 G polymorphism on MI. Seven studies investigated the relationship between t-PA I/D and MI.Results
This meta-analysis revealed that the PAI-1 4 G allele (4 G/4 G and 4 G/5 G genotype) was associated with an increased risk of MI compared with the 5 G allele in the overall population (OR = 1.094, 95% CI = 1.021 - 1.172, p = 0.011). The relative risks of MI for 4 G/4 G genotype was increased when compared to 5 G/5 G genotype and 5 G allele, with odds ratio at 1.157 (95% CI 1.015 - 1.320, p = 0.029) and 1.126 (95% CI = 1.015 - 1.249, p = 0.025). However, the results show that the 4 G/5 G polymorphism risk for MI was not associated with ethnicity stratification as Caucasian, Asian or African population. No substantial differences in the genotype distributions were observed in the MI group and control group along the lines of gender and age. After multivariable analysis t-PA I/D polymorphism showed no consistent association with MI.Conclusions
This study suggests that the 4 G/5 G polymorphism of PAI-1 may be a risk factor for MI in overall populations. 相似文献15.
Jiarong Wang Chengdi Wang Nan Chen Chi Shu Xiaojiang Guo Yazhou He Yanhong Zhou 《Thrombosis research》2014
Introduction
The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism was considered to be associated with risk of venous thromboembolism (VTE), while evidence remains inadequate. To provide a more accurate estimation of this relationship, we performed an updated meta-analysis of all eligible studies.Materials and Methods
A systematical search was performed in PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure (CNKI) and Cqvip databases to identify relevant studies published before March 6th 2014. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the fixed/random-effects model using Review Manager 5.1 and STATA 12.0.Results
A total of 34 studies with 3561 cases and 5693 controls were analyzed. Overall, significant association between the PAI-1 4G/5G variant and VTE risk in total population (dominant model: OR = 1.32, 95%CI: 1.13-1.54) was observed. And this variant was also related to the deep vein thrombosis risk (dominant model: OR = 1.60, 95%CI: 1.24-2.06, P = 0.0003). In the subgroup analyses on ethnicity, significant results were obtained in both Asians (dominant model: OR = 2.08, 95%CI: 1.29-3.35, P = 0.003) and Caucasians (dominant model: OR = 1.31, 95%CI: 1.10-1.56, P = 0.003). However, no significant association was found in patients with provoked VTE. In terms of subgroup analyses on co-existence of other thrombotic risk factors, the PAI-1 4G/5G polymorphism was significantly associated with VTE risk in patients with factor V Leiden mutation (dominant model: OR = 1.72, 95%CI: 1.17-2.53), but not in patients with cancer or surgery.Conclusion
Our findings demonstrate the role of PAI-1 4G/5G polymorphism being a risk candidate locus for VTE susceptibility, especially in patients with other genetic thrombophilic disorders. 相似文献16.
Xiao-Nan Liang Li Xie Jian-Wen Cheng Zhen Tan Jun Yao Qian Liu Wei Su Xue Qin Jin-Min Zhao 《Thrombosis research》2013
Background
The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH), but study results are controversial. The aim of this study was to derive a more precise estimation of the relationship between the PAI-1 4G/5G Gene polymorphism and ONFH by performing a meta-analysis.Methods
The meta-analysis was based on five eligible case-control studies involving 419 cases and 969 controls and summarized data indicating the association between PAI-1 polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association in the random-effects model or fixed-effects model.Results
A significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G4G + 4G5G vs. 5G5G (OR = 1.766, 95% CI 1.279–2.437, P = 0.001), 4G/4G vs. 4G/5G + 5G/5G (OR = 2.050, 95% CI 1.581–2.657, P = 0.000), 4G/4G vs. 5G/5G (OR = 2.553, 95% CI 1.345–4.846, P = 0.004), and 4G vs. 5G (OR = 1.758, 95% CI 1.236–2.500, P = 0.002). No significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G/5G vs. 5G/5G (OR = 1.327, 95% CI 0.939–1.877, P = 0.109).Conclusions
This meta-analysis suggested that 4G/5G polymorphism of the PAI-1 gene was a risk factor for ONFH. This study also suggests that the PAI-1 4G4G genotype may indicate a risk for ONFH. 相似文献17.
Introduction
Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.Materials and methods
The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.Results
15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR = 1.02, 95% CI = 0.83 - 1.26 for G versus A and OR = 0.96, 95% CI = 0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.Conclusion
These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development. 相似文献18.
Caroline Dubertret Claire Bardel Nicolas Ramoz Pierre-Marie Martin Jean-Charles Deybach Jean Adès Philip Gorwood Laurent Gouya 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Background
The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.Methods
We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.Results
Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.Conclusions
Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia. 相似文献19.
Xiao-Yu Xin Yan-Yan Song Jian-Fang Ma Cai-Ni Fan Jian-Qing Ding Guo-Yuan Yang Sheng-Di Chen 《Thrombosis research》2009,124(5):619-624
Introduction
Genetic studies restricted to young adult ischemic stroke patients may help in excluding the potentially confounding variables encountered with advanced age; thus, allowing a more precise risk evaluation derived from the inherited mutations alone. Through meta-analysis, this study was conducted to determine the genetic risk contributed by each susceptibility gene polymorphism, particularly in adult early-onset ischemic stroke patients.Materials and Methods
Electronic databases were searched for all the case-control studies relating to any candidate genes for ischemic stroke. The range of age was 18-50 years for cases. Fixed or random effects model was used depending on the heterogeneity between studies.Results
Twenty-six studies were finally included in this meta-analysis; these studies focused on 7 candidate genes. A significant but modest association was identified for 2 polymorphisms, namely, methylenetetrahydrofolate reductase (MTHFR) C677T (OR = 1.44, 95% CI = 1.14-1.80) and apolipoprotein E (ApoE) ε2-4 (OR = 2.53, 95% CI = 1.71-3.73). Although the pooled analysis for platelet glycoprotein Ia (GPIa) C807T showed a positive association (OR = 1.50, 95% CI = 1.10-2.05), the Egger's test indicated the existence of publication bias (t = 5.27, P > |t| = 0.034).Conclusions
Genetic abnormalities specific to homocysteine and lipid metabolism increase the risk for ischemic stroke at an early age. These data may offer important implications for future genetic association studies for stroke. 相似文献20.