Long-term stability of fibrinolytic factors stored at -80 °C

Introduction

Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits.

Materials and Methods

Plasma samples stored at -80 ^°C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n = 1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n = 1558) and re-analysed 2001 (n = 78) and 2005 (n = 828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1.

Results

Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R² = 0.01, PAI-1 antigen R² = 0.01 and tPA-PAI-1 complex R² = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R² 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R² 0.67 - 0.93).

Conclusions

This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.     

Arterial pressure oscillation and muscle sympathetic nerve activity after 20 days of head-down bed rest

Both spectral power within the low-frequency component, i.e., 0.04 to 0.15 Hz, of systolic pressure and muscle sympathetic nerve activity are increased during head-up tilt. The nerve activity during tilt is altered after space flight and exposure to simulated microgravity. In the present study, correlations of the low-frequency component and the nerve activity were analyzed before and after 20 days of − 6° of head-down bed rest. Measurements were performed at − 6° head-down bed rest, 0° (flat), and 30° and 60° head-up tilt (HUT). Mean arterial pressure during HUT was not different between pre- and post-bed rest, but muscle sympathetic nerve activity in post-bed rest significantly increased at tilt angles of − 6°, 0°, 30°, and 60° compared with those during pre-bed rest. The low-frequency component of systolic pressure also significantly increased during post-bed rest compared with pre-bed rest at tilts of 0°, 30°, and 60°. The nerve activity and the frequency component were linearly correlated for individual (r² = 0.51-0.88) and averaged (r² = 0.60) values when the values included both pre- and post-bed rest. Thus, the low-frequency component of systolic pressure could be an index of the muscle sympathetic nerve activity during tilt during pre- and post-bed rest.     

Measurement of Fibrinogen in Frozen Plasma

Several large studies have compared fibrinogen measurements determined over a particular time interval. These assays are subject to difficulties encountered by all laboratories on tests carried out over a period of time such as assay drift. To avoid this problem, plasma can be stored frozen and fibrinogen determined in a large number of samples simultaneously. However, a thorough comparison of measurements carried out in fresh and frozen plasma has not yet been performed. Fibrinogen concentration was therefore determined in fresh plasma samples and then at a later date in the same samples after storage at −70°C. A good correlation was observed between the two measurements, however, bias increased at the higher fibrinogen levels which are most critical in the determination of thrombotic risk. An increase in measurement error as a result of freezing was also observed. These effects may, therefore, be important considerations in future studies of this nature.     

Flow cytometric detection of endothelial microparticles (EMP): Effects of centrifugation and storage alter with the phenotype studied

Introduction

Endothelial microparticles (EMP) are released into the circulation in case of endothelial disturbance, and are therefore increasingly investigated as a biomarker reflecting disease activity. Numerous pre-analytic methods have been proposed for their flow cytometric enumeration, but standardization is still lacking. In this study we evaluated the influence of centrifugation and storage conditions on EMP quantification.

Materials and Methods

Platelet-poor plasma (PPP) from 10 healthy volunteers was prepared by centrifugation at 1 550 g for 20 minutes twice. A first aliquot of PPP was analyzed immediately, a second after storage at 4 °C for 7 hours. A third and fourth aliquot were snap-frozen and stored at -80 °C for 7 and 28 days. A final aliquot was further centrifuged at 10 000 g for 10 minutes and analyzed immediately. EMP were defined as CD31+CD42b-, CD62E+, CD144+ or CD144+CD105+ particles, smaller than 1.0 µm.

Results

High speed centrifugation led to a significant loss of CD31+CD42b- EMP (p = 0.004). A good correlation between PPP and high speed centrifuged PPP was only found for CD144+ EMP (Kendall tau b = 0.611, p = 0.025).Storage at 4 °C did not affect EMP quantification. However, freezing at -80 °C increased CD31+CD42b- and CD62E+ EMP counts, and lowered CD144+ EMP (p < 0.05). Nevertheless, the agreement among the different storage conditions was relatively good (Kendall coefficient of concordance > 0.487; p < 0.05).

Conclusion

The flow cytometric detection of EMP varies with the centrifugation protocol and the storage method used, and these changes also depend on the phenotype studied. The results of this study caution against comparing study results gathered with different EMP laboratory protocols.     

Aβ1–42 Detection in CSF of Alzheimer's disease is influenced by temperature: Indication of reversible Aβ1–42 aggregation?

Amyloid-beta 1–42 (Aβ1–42), peptide detectable in cerebrospinal fluid (CSF), has been extensively studied as diagnostic marker for Alzheimer's disease; however, results are variable. We investigated whether Aβ1–42 detection in CSF may be affected by handling temperature after lumbar puncture. CSF was collected from patients affected by probable AD (n = 27), other dementias (OD) (n = 24), or other neurological disorders without cognitive impairment (OND) (n = 23). After lumbar puncture, CSF samples were either maintained at 37 °C, or handled according to standard procedures and centrifuged at 4 °C for 10 min; thereafter, one aliquot was further stored at 4 °C and another at 37 °C, before freezing all samples 90 min later at − 80 °C, pending analysis. Aβ1–42 and total tau were determined using a commercially available sandwich enzyme-linked immunosorbent assay ELISA. Reduced Aβ1–42 and increased total tau CSF levels were confirmed as characteristic hallmarks of the OD and AD groups, providing standard measurement in samples stored at 4 °C before freezing. However, avoiding cooling or reheating CSF from 4 to 37 °C before freezing strikingly increased the Aβ1–42 concentration detectable in the AD group (P < 0.01), but not in control groups. The results indicate that a pool of Aβ1–42 cannot be detectable in the CSF of AD patients, because standard preanalytical cooling masks in some ways the epitope recognized by Aβ1–42 specific antibodies. Moreover, our study suggests that low temperature could induce Aβ1–42 conformational changes and multimeric aggregates in probable AD, but, more importantly, Aβ1–42 aggregation could be reversible.     

The fibrinogen gamma 10034C > T polymorphism is not associated with Peripheral Arterial Disease

Conversion of fibrinogen to fibrin plays an essential role in hemostasis and results in stabilization of the fibrin clot. Fibrinogen consists of three pairs of non-identical polypeptide chains, encoded by different genes (fibrinogen alpha [FGA], fibrinogen beta [FGB] and fibrinogen gamma [FGG]). A functional single nucleotide polymorphism (SNP) in the 3' untranslated region of the FGG gene (FGG 10034C > T, rs2066865) has been associated with deep venous thrombosis and myocardial infarction. Aim of the present study was to analyze the role of this polymorphism in peripheral arterial disease (PAD). The study was designed as case-control study including 891 patients with documented PAD and 777 control subjects. FGG genotypes were determined by exonuclease (TaqMan) assays. FGG genotype frequencies were not significantly different between PAD patients (CC: 57.3%, CT: 36.7%, TT: 5.8%) and control subjects (CC: 60.9%, CT: 33.5%, TT 5.6%; p = 0.35). In a multivariate logistic regression analysis including age, sex, smoking, diabetes, arterial hypertension and hypercholesterolemia, the FGG 10034 T variant was not significantly associated with the presence of PAD (Odds ratio 1.07, 95% confidence interval 0.84 - 1.37; p = 0.60). The FGG 10034C > T polymorphism was furthermore not associated with age at onset of PAD. We conclude that the thrombophilic FGG 10034 T gene variant does not contribute to the genetic susceptibility to PAD.     

Quasi-classical trajectory study of the dynamics of the reaction F + DCl (v = 0, j = 0) → DF + Cl

Theoretical studies of the dynamics of the reaction F + DCl(v = 0, j = 0) → DF + Cl are performed with quasi-classical trajectory (QCT) method on a recently computed 1²A′ ground-state surface reported by Deskevich et al. [33]. The calculated QCT reaction probabilities for total angular momentum J = 0 are in good agreement with earlier quantum wave packet results calculated by Sun et al. [35] over the collision energy range from 4 to 30 kcal/mol. The integral cross-sections as functions of collision energy are presented. The differential cross-sections are governed by the direct reaction dynamics that follow the minimum energy path at both low and high collision energies. The rotational angular momentum vectors j′ of the product DF are not only aligned, but also oriented along the y-axis. The degrees of alignment and orientation of DF in reaction F + DCl(v = 0, j = 0) → DF + Cl differ from that of HF in reaction F + HCl(v = 0, j = 0) → HF + Cl. The differences in vector properties of DF in reaction F + DCl between that of HF in reaction F + HCl may be attributed to the difference in the mass factor in the two reactions.     

Stereodynamics of the reaction H + LiH (v = 0, j = 0) → H2 + Li and its isotopic variants

Quasi-classical trajectory (QCT) method is used to calculate the stereodynamics of the reactions H + LiH (v = 0, j = 0) → H₂ + Li and its isotopic variants based on the ground electronic state potential energy surface (PES) reported by Prudente et al. [14]. The reactive probabilities of the title reactions are computed. We also observed the changes of vector correlations and four generalized polarization-dependent differential cross-sections (PDDCSs) at different collision energies, and we compared the stereodynamics among different isotopic variants of the title reactions. The product polarization distribution of the title reactions exhibits distinct difference which may arise from different mass combinations or kinetic energies.     

A new method for visualization of endothelial cells and extravascular leakage in adult mouse brain using fluorescein isothiocyanate

The ability to successfully cryopreserve neural cells would represent an important advance with benefits to neural tissue engineering, neural transplantation, and neuroscience research. We have examined key factors responsible for damage to rat embryonic neural cells during cryopreservation using a two-step temperature profile, with an emphasis on the effects of cooling rate and plunge temperature. Our results indicate that the initial addition of 8% dimethyl sulfoxide (DMSO) and seeding of extracellular ice do not significantly decrease viable cell yield. However, subsequent freezing resulted in significant cell losses for all profile parameter combinations examined. A maximum post-thaw survival of 56% (compared to unfrozen controls) was observed after cooling at 2 °C/min to −80 °C followed by direct immersion in liquid nitrogen. Single-step removal of DMSO after thawing was associated with an additional 40-70% loss of viable cells, and the number of viable cells was further reduced by approximately 70% after 2 days of cell culture (resulting in a net viable cell yield of 9.6 ± 0.4%). Nonetheless, the cryopreserved neurons that did survive displayed a normal morphology, including formation of neurites. Trends in neuronal viability conformed with predictions of existing theoretical models of cell freezing, with reduced survival for rapid cooling rates or high plunge temperatures (attributable to intracellular ice formation), and decreasing viability with increasing profile duration (consistent with the known effects of cell dehydration at suboptimal cooling rates). These observations suggest that neural cells are good candidates for further refinement of freezing profile design using a physics-based approach to parameter optimization.     

Noninvasive measurement of human brain temperature adjacent to arteriovenous malformation using 3.0 T magnetic resonance spectroscopy

Object

The brain temperature at rest is determined by the balance between heat produced by cerebral energy turnover, which is identical to cerebral metabolism, and heat that is removed, primarily by cerebral blood flow. The present study investigated whether brain temperature measured by proton magnetic resonance (MR) spectroscopy can detect cerebral hemodynamic impairment in patients with arteriovenous malformations (AVMs) as shown by single photon emission computed tomography (SPECT).

Methods

Brain temperature, cerebral blood flow, and cerebrovascular reactivity were measured using proton MR spectroscopy and SPECT in five healthy volunteers and six patients with AVMs. Regions of interest were selected adjacent to the AVMs and in the corresponding contralateral region.

Results

Brain temperature around AVMs was calculated in all subjects using MR spectroscopy. The mean brain temperature in volunteers was 37.1 ± 0.41 °C. A significant correlation was observed between brain temperature ratio (affected side/contralateral side) and cerebrovascular reactivity ratio (affected side/contralateral side) (r = −0.82, p = 0.0480).

Conclusion

Brain temperature measured by proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with AVMs. Further investigations regarding the relationships between brain temperature and clinical feature in patients with AVMs are needed.     

Prothrombin time, activated partial thromboplastin time and dilute Russell's Viper Venom times are not shorter in patients with the prothrombin G20210A mutation, and dilute Russell's Viper Venom time may be longer

Introduction

Prothrombin G20210A (PT20210) carriers have increased prothrombin levels and increased risk for venous thrombosis. We hypothesized PT20210 carriers would have decreased PT, aPTT, and dRVVT clotting times.

Methods

We reviewed 1186 thrombotic risk panels that included PT, aPTT, dRVVT, and PT20210 genotype with potential confounding variables, excluding samples consistent with anticoagulant therapy or lupus anticoagulant presence. We examined relationships of PT20210 with PT, aPTT, and dRVVT correcting for covariates using multivariate regression. We confirmed associations in 1876 separate panel results and a group of homozygotes for PT20210 and used general linear models to determine if associated tests predict PT20210 status.

Results

Neither PT, aPTT, nor dRVVT was shorter in PT20210 carriers. Contrary to our hypothesis, PT20210 was significantly associated with higher dRVVT (p = 0.001), but not PT or aPTT. dRVVT differences were significant in a replicate sample p = 0.035 and an additional sample of PT20210 homozygotes (p = 0.02). Of all variables available, only dRVVT predicted PT20210 carrier status (p = 0.0008, AUC = 0.64).

Conclusions

We observed an association between longer dRVVT and the prothrombin G20210A mutation in a retrospective observational study. These findings merit further study in large well-characterized clinical cohorts and laboratory research experiments.     

Evaluation and performance characteristics of the Q Hemostasis Analyzer, an automated coagulation analyzer

The Q Hemostasis Analyzer (Grifols, Barcelona, Spain) is a fully-automated random-access multiparameter analyzer, designed to perform coagulation, chromogenic and immunologic assays. It is equipped with a cap-piercing system. The instrument was evaluated in a hemostasis laboratory of a University Hospital with respect to its technical features in the determination of coagulation i.e. prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time, fibrinogen and single coagulation factors V (FV) and VIII (FVIII), chromogenic [antithrombin (AT) and protein C activity] and immunologic assays [von Willebrand factor antigen (vWF:Ag) concentration], using reagents from the analyzer manufacturer. Total precision (evaluated as the coefficient of variation) was below 6% for most parameters both in normal and in pathological ranges, except for FV, FVIII, AT and vWF:Ag both in the normal and pathological samples. No carryover was detected in alternating aPTT measurement in a pool of normal plasma samples and in the same pool spiked with unfractionated heparin (> 1.5 IU/mL). The effective throughput was 154 PT, 66 PT/aPTT, 42 PT/aPTT/fibrinogen, and 38 PT/aPTT/AT per hour, leading to 154 to 114 tests performed per hour, depending of the tested panel. Test results obtained on the Q Hemostasis Analyzer were well correlated with those obtained on the ACL TOP analyzer (Instrumentation Laboratory), with r between 0.862 and 0.989. In conclusion, routine coagulation testing can be performed on the Q Hemostasis Analyzer with satisfactory precision and the same apply to more specialized and specific tests.     

Effect of VKORC1 - 1639 G > A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients

Introduction

To establish individualized warfarin therapy, we investigated the contribution of genetic variations of vitamin K epoxide reductase complex subunit 1 gene (VKORC1) - 1639 G > A and Cytochrome P450 2C9 gene (CYP2C9) and clinical factors on warfarin sensitivity in Japanese patients.

Materials and Methods

Genetic analyses of VKORC1 - 1639 G > A and CYP2C9 ?2, ?3, and ?4 were performed in 259 Japanese patients and 341 healthy subjects. We selected 259 patients who have been prescribed warfarin with a 1.5-3.0 range of prothrombin time normalized as an international normalized ratio for at least 3 months and investigated factors that contribute to individual variability in warfarin dose. Furthermore, multivariate analysis was performed to investigate a warfarin dosing algorithm.

Results and Conclusions

There were great inter-individual differences in warfarin maintenance dose in 259 patients, ranging from a minimum dose of 0.75 mg/day to a maximal dose of 8.00 mg/day. VKORC1 - 1639 G > A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variability. The dosing algorithm of warfarin maintenance dose was investigated by multivariate linear regression. The regression equation was able to account for 33.2% (R²_Adj = 0.332) of the overall variability in warfarin dose.     

Ab initio molecular dynamics simulation on SiN + CH and SiC + NH reactions

The production mechanism for interstellar silicon compounds SiCN, its isomer SiNC, hydrogen cyanide HCN and its isomer HNC from the neutral–neutral reactions SiN + CH and SiC + NH was studied using ab initio molecular dynamics. Classical trajectories were calculated by the direct dynamics simulation technique at the B3LYP/6-311++G(d, p) level of theory. Reaction channels were checked by single-point energy calculations on intermediates and transition states at the B3LYP/6-311++G(3df, 3pd) level of theory and by intrinsic reaction coordinate calculations on reaction coordinates at the B3LYP/6-311++G(d, p) level of theory. More than 100 trajectories were integrated for both reactions. We confirmed that the reaction SiN + CH mostly produces SiNC and HCN, and the reaction SiC + NH mostly produces HNC and SiNH. The reaction processes were examined from the viewpoint of minimum energy path.     

Decline in platelet microparticles contributes to reduced hemostatic potential of stored plasma

Introduction

In an effort to administer life-saving transfusions quickly, some trauma centers maintain thawed plasma (TP). According to AABB, TP is approved for transfusion for up to five days when stored at 1 - 6 °C. However, the alterations in microparticles (MP) contained in the plasma, which are an integral component of plasma's hemostatic capacity, are not well characterized. We report on MP changes in TP between its initial thaw (FFP-0) and five days (FFP-5) of storage.

Materials and Methods

FFP units (n = 30) were thawed at 37 °C and kept refrigerated for five days. Phenotypes of residual cells, which include platelets, erythrocytes, leukocytes, monocytes, endothelial cells, and MP counterparts of each cell type, were analyzed by flow cytometry. Functional assays were used for MP procoagulant activity, plasma thrombin generation, and clotting properties (thromboelastography).

Results

In FFP-0 the majority (94%) of residual cells were platelets, along with significant levels of platelet MPs (4408 × 10³/L). FFP-5 showed a decline in MP count by 50% (p < 0.0001), and procoagulant activity by 29% (p < 0.0001). FFP-5 exhibited only 54% (p < 0.0001) of the potential for thrombin generation as FFP-0, while thromboelastography indicated a slower clotting response (p < 0.0001) and a longer delay in reaching maximum clot (p < 0.01). Removal of MP by filtration resulted in reduced thrombin generation, while the MP replacement restored it.

Conclusions

Decline in MP with storage contributes to FFP-5's reduced ability to provide the hemostatic potential exhibited by FFP-0, suggesting the presence of platelet MPs in freshly TP may be beneficial and protective in the initial treatment of hemorrhage.     

A theoretical study for the influence of coverage on Li,Na and K adsorption on Co(0 0 0 1)

Periodic density-functional theory calculations of Li, Na and K adsorbed on Co(0 0 0 1) have been performed up to the coverage of 0.5 ML. Calculated results indicate that top, bridge and hollow sites are degenerated with almost identical adsorption energies for all considered cases. The adsorption energies, optimized structures, work function and electron charge density changes are discussed. We have also studied the possibility of substitutional adsorption and the results are compared with that on-surface adsorption, in particular for the p(2 × 2) overlayer.     

The lazaroid U-83836E improves the survival of rat embryonic mesencephalic tissue stored at 4°C and subsequently used for cultures or intracerebral transplantation

We assessed the effects of addition of the lazaroid U-83836E to a preservation medium on the survival of rat dopamine neurons stored before culturing or intracerebral transplantation. Embryonic ventral mesencephalic tissue was preserved at 4°C for 8 days with or without the addition of 0.3 μM of U-83836E to a chemically defined “hibernation” medium. Freshly dissected mesencephalic tissue was used in control groups. For culture experiments, the mesencephalic tissue was dissociated and grown in serum-containing medium. Following 24–48 h in vitro, the number of dopamine neurons in cultures derived from tissue hibernated without the lazaroid was 40% of fresh control, compared with 67% of control in cultures prepared from tissue stored in the presence of U-83836E. When mesencephalic tissue was transplanted to the dopamine-depleted striatum of hemiparkinsonian rats following 8 days storage at 4°C in a medium without U-83836E, the mean number of surviving dopamine neurons in the grafts was significantly reduced to 40% of control. In contrast, grafts of tissue which had been hibernated in U-83836E-containing medium contained as many dopamine neurons as transplants of freshly dissected tissue. High yields of surviving grafted dopamine neurons were correlated to a significantly faster onset of functional recovery of amphetamine-induced motor asymmetry. We conclude that the storage period for rat mesencephalic tissue can be prolonged up to 8 days when using lazaroid-supplemented hibernation medium. As lazaroids have undergone clinical safety testing, the application of lazaroids for tissue storage in clinical transplantation trials can be envisaged.     

Computational evidence of preferred energy and preferred binding energy in the formation of “1 + 1” versus “2 + 2” macrocyclic Schiff base complexes

This work reports a theoretical study on “1 + 1” versus “2 + 2” cyclocondensation reactions between 2,6-diacetylpyridine and 3,6-dioxaoctane-l,8-diamine in the presence of Mg(II) and Pb(II) metal ions. The results of calculations at DFT(B3LYP) level of theory using LanL2DZ, SDD and CEP-121G basis sets were consistent with the experimental observations and all showed that “1 + 1” and “2 + 2” macrocyclic Schiff base complexes are preferred products for Mg(II) and Pb(II) metal ions, respectively. It was shown that the prediction of the type of cyclocondensation reaction is possible if we calculate a “preferential energy” and/or a “preferential binding energy” for one of the corresponding products.     

Use of MRI for measuring structures in frozen postmortem brain

A method was developed for magnetic resonance imaging (MRI) of human autopsy brains stored long-term at −70°C. Scanning brains at temperatures between −70 and −8°C gave minimal MRI signals consistent with protons having limited freedom of movement at low temperature. Raising brain temperature improved the signal such that scanning at −1°C generated images with good in-plane resolution, grey/white matter contrast, and fine detail of cortical sulcal/gyral patterns. To validate the method, volume and area measurements were made using computerized image analysis on stored digital images of 14 brains from adult subjects of both genders and various ages. The data confirmed that brain volume was inversely correlated with age, and female subjects had smaller brains. This is a valuable new method for acquiring morphometric data from previously unscanned pathologic brains that are to be used for neurochemical and molecular investigations.     

Endothelial nitric oxide synthase 894 G > T polymorphism and thrombotic disease: A Meta-Analysis of 17 studies involving 8808 subjects

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.