Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head: A Meta-analysis

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.     

Influence of the β-fibrinogen-455G/A polymorphism on development of ischemic stroke and coronary heart disease

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.     

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.     

ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: a meta-analysis

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.     

Trauma exposure,posttraumatic stress disorder and risk for alcohol,nicotine, and marijuana dependence in Israel

Background

Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TE) and substance dependence.

Objectives

This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association.

Method

1317 Jewish Israeli household residents completed in-person structured interviews assessing TE, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007 and 2009. Regression analyses examined associations among TE, PTSD, and substance dependence.

Results

In the full sample, mean number of traumatic events was 2.7 (sd = 2.2), with 83.7% experiencing at least one event. In the full sample, mean number of PTSD symptoms was 2.5 (sd = 3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR = 1.3; 95% CI = 1.2–1.4) and nicotine (OR = 1.2; 95% CI = 1.1–1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR = 3.1; 95% CI = 1.6–6.0) and nicotine (OR = 1.9; 95% CI = 1.2–2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR = 1.2; 95% CI = 1.1–1.3), nicotine (OR = 1.1; 95% CI = 1.1–1.2), and marijuana (OR = 1.1; 95% CI = 1.04–1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR = 3.4; 95% CI = 2.1–5.5), nicotine (OR = 2.2; 95% CI = 1.4–3.4), and marijuana (OR = 2.6; 95% CI = 1.2–5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TE effect on alcohol (46%) and nicotine dependence (31%).

Conclusion

Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana dependence was only significantly related to PTSD symptoms. Clinicians and researchers should separately assess different types of dependence among trauma-exposed individuals both with and without PTSD symptoms.     

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.     

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study

Objective

To investigate the association between dopaminergic polymorphisms [DRD2 −141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia.

Methods

Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD) = 36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD) = 40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There was a significant difference in genotype distribution for the DRD2 −141C Ins/Del polymorphism [(χ² (2) = 12.35, corrected p = 0.012]. The − 141C Del allele was more common in patients than in controls [0.19 vs. 0.13; χ² (1) = 9.14, corrected p = 0.018, OR (95% CI) = 1.57 (1.17–2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald = 9.56 (4), p = 0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR = 0.51 (95% CI = 0.30–0.89), p = 0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR = 2.45 (95% CI = 1.16–5.17), p = 0.019] and Gly/Gly [OR = 3.80 (95% CI = 1.24–11.63), p = 0.019].

Conclusions

This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.     

The impact of childhood trauma on depression: Does resilience matter? Population-based results from the Study of Health in Pomerania

Objective

Data suggests that traumatic experiences at early age contribute to the onset of major depressive disorder (MDD) in later life. This study aims at investigating the influence of dispositional resilience on this relationship.

Methods

Two thousand and forty-six subjects aged 29–89 (SD = 13.9) from a community based sample who were free of MDD during the last 12 months prior to data collection were diagnosed for Lifetime diagnosis of MDD by the Munich-Composite International Diagnostic Interview (M-CIDI) according to DSM-IV criteria. Childhood maltreatment (CM) and resilience were assessed with the Childhood Trauma Questionnaire (CTQ) and the Resilience-Scale (RS-25).

Results

Both CM (OR = 1.03, 95% CI [1.02, 1.04], P < .000) and resilience (OR = 0.98, 95% CI [0.98, 0.99], P < .000) were associated with MDD later in life. The detrimental effects of low resilience on MDD were not only especially prominent in subjects with a history of CM (OR = 3.18, 95% CI [1.84, 5.50], P < .000), but also effective in subjects without CM (OR = 2.62, 95% CI [1.41, 4.88], P = .002).

Conclusions

The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of child abuse and neglect.     

Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit

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.     

Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis

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.     

A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes

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.     

Association of tissue plasminogen activator and plasminogen activator inhibitor polymorphism with myocardial infarction: A meta-analysis

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.     

Association of depression symptoms with quality of life and chronic artery vasculopathy: A cross-sectional study in heart transplant patients

Objective

Depression represents a relevant co-morbidity in patients with chronic heart disease and may diminish the overall success for long-term survival after heart transplantation (HTx). This study aimed to assess the prevalence of depression symptoms in long-term HTx survivors, and to compare depressive patients to those without depression with respect to chronic artery vasculopathy (CAV).

Methods

A sample of 203 HTx patients, median 11.5 (IQR 7–17) years after transplant, provided detailed data of depression symptoms, and other psychosocial symptoms including anxiety, family support, professional re-integration, and health-related quality of life (HRQoL). Data were analyzed for an association with CAV.

Results

Overall, 14.8% patients (95% CI: 10.2–20.4) showed relevant depression symptoms. No significant differences were seen between non-depressed vs. depressed patients with respect to demographics, clinical variables, and cardiovascular risk factors. Anxiety was prevalent in 9.0% (95% CI: 5.4–13.9) of the sample. Depression symptoms showed impaired HRQoL in the SF-36 physical (P = .012) and psychosocial (P = .0001) components. CAV was prevalent in 34.0% (95% CI: 27.5–41.0), and depression symptoms and CAV were not significantly associated. CAV-patients did not report their physical HRQoL being lower relative to those without CAV (P = .40). Multivariate analysis revealed overweight BMI (OR = 2.20; P = .04), longer time since transplant (OR = 1.10; P = .001), and older age (OR = 1.04; P = .01) being associated with CAV.

Conclusion

Depression symptoms are prevalent in long-term survivors after HTx, and psychological impairments decrease patients' perceptions of HRQoL. More research seems necessary to identify the inter-relationship between depression symptoms and CAV, in order to develop targeted interventions to overcome this problem.     

Association between adiponectin gene polymorphisms and coronary artery disease across different populations

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.     

Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy

Rationale

Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in mitochondrial fatty acid oxidation, which is essential for energy production during simultaneous glucose sparing and a requirement for major energy supply, such as prolonged fasting or exercise. When infants require more energy than provided by the glycolytic system, they rely on the mitochondrial fatty acid oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2 polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity. The F352C variant results in energy crisis at high temperature and is suspected as a risk factor for acute encephalopathy. However, a relationship between CPT2 gene polymorphism and SUDI has not been described.

Methods

Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers.

Results

The frequency of the C allele was significantly higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.05–2.92, p = 0.030). The frequency of the F352C homozygote was significantly higher in the SUDI group than in control group (11.1% vs 3.5%, OR = 3.45, 95% CI = 1.11–10.73, p = 0.036).

Conclusion

The F352C CPT2 variant might be a genetic risk factor for SUDI.     

The association between non-motor symptoms in Parkinson's disease and age at onset

Objective

Age at onset is likely to be related to a wide range of problems in Parkinson's disease (PD), including cardinal motor features, motor complications and non-motor symptoms (NMS). This study investigated the effect of the age at onset on NMS.

Methods

Two hundred and thirty patients were examined and classified into one of three groups based on age at onset: early onset PD (EOPD) group (<45 years), middle-age onset group (45–64 years) and old-age onset group (≥65 years). The trends relating to NMS were compared across the three groups. The EOPD and old-age onset groups were separately studied to determine their association to the appearance of non-motor features using logistic regression analysis.

Results

There were upward trends in the occurrence of dribbling (P = 0.009; all P values are stated for trend), impaired taste/smelling (P = 0.016), constipation (P = 0.006), urinary urgency (P = 0.002), nocturia (P = 0.018), hallucinations (P = 0.016) and acting out during dreams (P = 0.011) with the increase of age at onset. Older age at onset is an independent risk factor for dementia (OR = 8.42, CI 3.16–22.44), dribbling (OR = 4.14, CI 1.93–8.87), impaired taste/smelling (OR = 2.23, CI 1.20–4.13), constipation (OR = 3.42, CI 1.88–6.24), incomplete bowel emptying (OR = 2.23, CI 1.19–4.20), urinary urgency (OR = 2.58 CI 1.46–4.57), nocturia (OR = 2.65, CI 1.49–4.71), hallucinations (OR = 5.32, CI 1.78–15.97), dizziness (OR = 3.03, CI 1.59–5.79), falling (OR = 3.60, CI 1.67–7.77), insomnia (OR = 2.29, CI 1.28–4.11), intense vivid dreaming (OR = 2.10, CI 1.21–3.66) and acting out during dreams (OR = 2.23, CI 1.24–4.01).

Conclusions

PD patients with different ages at onset present clinically different symptoms in terms of NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms, autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.     

Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

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.     

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.     

Perceived weight in youths and risk of overweight or obesity six years later

Objective

To examine the association between perceived overweight in adolescents and the development of overweight or obesity later in life.

Methods

This paper uses data from a prospective, two-wave cohort study. Participants are 2445 adolescents 11–17 years of age who reported perceived weight at baseline and also had height and weight measured at baseline and at follow-up six years later sampled from managed care groups in a large metropolitan area.

Results

Youths who perceived themselves as overweight at baseline were approximately 2.5 times as likely to be overweight or obese six years later compared to youths who perceived themselves as average weight (OR = 2.45, 95% CI = 1.77–3.39), after adjusting for weight status at baseline, demographic characteristics, major depression, physical activity and dieting behaviors. Those who perceived themselves as skinny were less likely to be overweight or obese later (OR = 0.36, 95% CI = 0.27–0.49).

Conclusions

Perceived overweight was associated with overweight or obesity later in life. This relationship was not fully explained by extreme weight control behaviors or major depression. Further research is needed to explore the mechanism involved.     

A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect

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.