脂蛋白脂酶Ser447Term多态性和卒中相关危险因素相互作用对缺血性脑卒中发病的影响

目的 本研究旨在探讨脂蛋白脂酶(LPL) Ser447Term多态性与一些常见的卒中危险因素之间的相互影响.方法 检测704个汉族缺血性脑卒中患者的基因型,根据这些患者所具有的卒中相关危险因素将其分为2型糖尿病组、高血压组、吸烟组和高脂血症组.应用聚合酶链反应-限制性片段长度多态性方法对Ser447Term的多态性进行基因分型.结果 卡方(x2)检验结果显示:在有糖尿病史的卒中患者中Ser447Term G等位基因的携带率显著高于无糖尿病史的卒中患者(x2=7.25,P=0.007,OR=1.78,95％ C/I.18～ 2.68).这样的相关性并未在具有其他3个卒中相关的危险因素的患者中观察到.结论 LPL基因多态性与糖尿病的联合作用可能促成缺血性卒中的一个亚组的发病.     

Lack of evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke: A meta-analysis of 8,800 subjects

Introduction

Epidemiological studies have evaluated the association between factor XIII-A (FXIII-A) Val34Leu polymorphism and risk of ischemic stroke, but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methods

Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale, NOS) were independently conducted in duplicate. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by funnel plot, Egger's regression test and Begg's test. Sensitivity analysis was conducted by limiting the meta-analysis to the high quality studies (NOS score≥8).

Results

A total of 16 studies including 3,807 cases and 4,993 controls were combined showing no evidence of association between FXIII-A Val34Leu polymorphism and ischemic stroke (for Val/Leu vs. Val/Val : OR = 0.95, 95%CI = 0.77-1.16; for Leu/Leu vs. Val/Val: OR = 0.90, 95%CI = 0.73-1.11; for dominant model: OR = 0.97, 95%CI = 0.81-1.17; for recessive model: OR = 0.95, 95%CI = 0.77-1.17). In the subgroup analyses by study design, ethnicity and specific subtypes (small-vessel occlusive ischemic stroke and large-artery atherosclerotic ischemic stroke ), there was lack of evidence for the association.

Conclusions

This meta-analysis indicates that there is no evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke.     

Association of ADIPOQ gene polymorphisms and coronary artery disease risk: a meta-analysis based on 12 465 subjects

Introduction

Coronary artery disease (CAD) is one of the most common cardiovascular diseases and is a major cause of morbidity and mortality worldwide. Various researchers have investigated the role of ADIPOQ gene in the risk of CAD, yet their results have been inconsistent.

Methods

To evaluate the association between ADIPOQ genetic polymorphisms and CAD risk, relevant studies published before October 2011 were identified by searching PubMed and EMBASE. Studies were selected using previously defined criteria. The strength of the relationship between the four single nucleotide polymorphisms (SNPs) of the ADIPOQ gene and CAD risk was assessed using odds ratios (ORs).

Results

A total of 12 465 subjects from 17 case-control studies were identified in the present study. Based on the relevant studies, it was determined that the risk of CAD was not associated with rs2241766 in any genetic model. Increased risk of CAD was associated with rs266729 in allele contrast (1.11, [1.03, 1.20]) and dominant genetic model (1.15, 95%CI: [1.05, 1.27]); increased risk of CAD was also associated with rs822395 in additive (1.63, 95%CI: [1.19, 2.22]) and recessive genetic model (1.71, 95%CI: [1.27, 2.30]). It was further determined that the rs1501299 polymorphism reduced the risk of CAD in the additive (0.80, 95%CI: [0.67, 0.94]) and recessive genetic model (0.81, 95%CI: [0.68, 0.95]). In the stratified analysis, significant associations were found in Asian subjects for rs266729 and in Caucasian subjects for rs1501299.

Conclusion

There is an association between ADIPOQ gene polymorphisms and CAD risk. Different SNPs of the ADIPOQ gene have different associations with CAD risk, and appear to increase risk in individuals of Asian ethnicity while decrease the CAD risk in Caucasians. However, the overall strength of association was mild to moderate.     

Combination oral antiplatelet therapy may increase the risk of hemorrhagic complications in patients with acute ischemic stroke caused by large artery disease

Introduction

The association between the frequency or severity of bleeding complications and combination antiplatelet therapy for acute stroke treatment is not understood in detail. This retrospective study investigated whether combination oral antiplatelet therapy for cases with acute ischemic stroke due to large artery disease increased the incidence of hemorrhagic complications.

Materials and Methods

We reviewed 1335 consecutive patients who were admitted to our department within 7 days of the onset of an ischemic stroke or transient ischemic attack between April 2005 and November 2009. We enrolled 167 patients with > 50% stenosis or occlusion in culprit major vessels and who were administered oral antiplatelet agents within 48 hours of admission. Hemorrhagic complications were classified according to the bleeding severity index. We studied the association between the incidence and severity of hemorrhagic complications during hospitalization and the clinical characteristics, including antiplatelet therapy.

Results

Fifty-nine and 108 patients were treated with only 1 antiplatelet agent and combination antiplatelet agents, respectively. Fourteen patients developed bleeds (3 major and 11 minor), and all of the major bleeds occurred in those given combination agents. The proportion of patients receiving combination agents was significantly higher in those with significant bleeds. Multivariate logistic regression analysis revealed that being older and receiving combination agents were independent predictors for significant bleeds during hospitalization.

Conclusions

Despite the retrospective nature of this study, our findings suggest that the incidence of hemorrhagic complications increases in patients with acute ischemic stroke treated with combination antiplatelet agents.     

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and risk of venous thromboembolism: A meta-analysis

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 6^th 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.     

No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes

Introduction

The ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke.

Materials and methods

The study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70 years, and 600 matched controls. Patients were classified according to the TOAST criteria.

Results

There was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype.

Conclusions

The findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.     

Joint effects of eNOS gene T-786C and ADH2 Arg47His polymorphisms on the risk of premature coronary artery disease

INTRODUCTION: Both T-786C mutation in endothelial nitric oxide synthase (eNOS) gene and alcohol dehydrogenase (ADH) gene polymorphism such as ADH3 gamma1/gamma2 have been reportedly associated with coronary artery disease (CAD). Since ADH2 Arg47His polymorphism is common in Asian population, the aim of this present study was to assess the interaction between eNOS gene T-786C and ADH2 Arg47His polymorphisms on premature CAD risk. MATERIALS AND METHODS: Hospital-based case-control study was conducted with 167 premature CAD and 235 late-onset CAD patients. Polymerase chain reaction restriction fragment length polymorphism was used to detect the polymorphisms. Multivariate logistic regression model was performed to adjust the potential confounders and estimate odds ratios (ORs) with 95% confidence intervals (CIs). Synergy index (S) was the measure to assess the interaction as departure from additivity. RESULTS: After the adjustment for the potential confounders, and compared with the carriers of TT and Arg/Arg as the reference, the ORs with 95% CIs in parentheses of premature CAD were that 1.13 (0.19-6.59) for CT or CC and Arg/Arg carriers; 2.24 (0.77-6.49) for TT and Arg/His or His/His carriers; 4.18 (1.32-13.22) for CT or CC and Arg/His or His/His carriers, respectively. Based on those ORs, S was 2.32 (95% CI: 0.37-14.72). CONCLUSIONS: The mutant genotypes of eNOS gene T-786C mutation and the fast form of ADH2 Arg47His polymorphism had an additive interaction on the risk of premature CAD in Chinese population. Further investigations with big sample size are necessary for confirming this additive interaction.     

Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia

Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value = 0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes.