Early exposure to maternal stress and risk for atopic dermatitis in children: A systematic review and meta-analysis.

BACKGROUND: The incidence of atopic dermatitis (AD) in children is increasing. Early exposure to stress factors may be associated with the AD development. This study aimed to summarize studies that reported an association between stress exposure and AD development in later life. METHODS AND FINDINGS: A comprehensive literature search was performed using online databases (PubMed, EMBASE, PsycINFO, and Web of Science) for articles published up to May 1, 2023. Eligible studies were screened and selected based on the inclusion criteria. We incorporated cohort or case-control studies published in English which explored the relationship between stress experienced by parents or children and AD. The pooled odds ratio (OR) was calculated according to the type of stress using a random-effects model. Twenty-two studies were included. AD was related to maternal distress (OR 1.29, 95% Confidence Interval [CI]: 1.13-1.47), maternal anxiety (OR 1.31, 95% CI: 1.18-1.46), and negative life events (OR 2.00, 95% CI: 1.46-2.76). Maternal depression during pregnancy was associated with AD (OR 1.21, 95% CI: 1.09-1.33), whereas no significant association was found for postpartum depression. Research on stress experienced by paternal or children is scare. CONCLUSIONS: Early maternal stress may potentially elevate the risk of AD in their offspring. Importantly, rigorously designed studies are required to corroborate the link between maternal stress and AD in children. These studies should aim to gather insights about the impact of stress during specific trimesters of pregnancy, postnatal stress, and paternal stress, and to identify potential prevention strategies.

Cumulative evidence for association of sepsis and retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease affected by multiple factors such as infection and preterm birth. The role of sepsis in the development of ROP remains controversial. This systematic review and meta-analysis aimed to identify the impact of sepsis on ROP. METHODS: The PubMed, Embase, and Cochrane Library databases were searched using terms related to sepsis and ROP. Cohort or case-control studies that reported the association of sepsis and ROP were eligible. The odds ratios (ORs) together with the 95% confidence interval (CI) were extracted from the studies or computed by authors if not provided. RESULTS: Thirty-four studies were ultimately included in this meta-analysis. The pooled results showed that sepsis increased the risk for the development of any stage ROP (OR = 2.16; 95% CI: 1.65-2.82). Both early onset (OR = 2.50; 95% CI: 1.97-3.18) and late-onset (OR = 1.37; 95% CI: 1.22-1.55) sepsis were associated with severe ROP. Furthermore, both bacterial sepsis (OR = 1.74; 95% CI: 1.21-2.50) and fungal sepsis (OR = 2.96; 95% CI: 2.05-4.28) were also found to be associated with severe ROP. CONCLUSION: Sepsis increased the risk of any stage ROP, especially for the severe ROP. Further high-quality clinical studies are needed to eliminate heterogeneity and publication bias to validate these findings.

Educational efficacy of high-fidelity simulation in neonatal resuscitation training: a systematic review and meta-analysis.

BACKGROUND: The training of neonatal resuscitation is an important part in the clinical teaching of neonatology. This study aimed to identify the educational efficacy of high-fidelity simulation compared with no simulation or low-fidelity simulation in neonatal resuscitation training. METHODS: The PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Chinese databases (CBM, CNKI, WanFang, and Weipu), ScopeMed and Google Scholar were searched. The last search was updated on April 13, 2019. Studies that reported the role of high-fidelity simulation in neonatal resuscitation training were eligible for inclusion. For the quality evaluation, we used the Cochrane Risk of Bias tool for RCTs and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for non-RCTs. A standardized mean difference (SMD) with a 95% confidence interval (CI) was applied for the estimation of the pooled effects of RCTs. RESULTS: Fifteen studies (10 RCTs and 5 single arm pre-post studies) were ultimately included. Performance bias existed in all RCTs because participant blinding to the simulator is impossible. The assessment of the risk of bias of single arm pre-post studies showed only one study was of high quality with a low risk of bias whereas four were of low quality with a serious risk of bias. The pooled results of single arm pre-post studies by meta-analysis showed a large benefit with high-fidelity simulation in skill performance (SMD 1.34; 95% CI 0.50-2.18). The meta-analysis of RCTs showed a large benefit in skill performance (SMD 1.63; 95% CI 0.49-2.77) and a moderate benefit in neonatal resuscitation knowledge (SMD 0.69; 95% CI 0.42-0.96) with high-fidelity simulation when compared with traditional training. Additionally, a moderate benefit in skill performance (SMD 0.64; 95% CI 0.06-1.21) and a small benefit was shown in knowledge (SMD 0.39; 95% CI 0.08-0.71) with high-fidelity simulation when compared with low-fidelity simulation. CONCLUSIONS: Improvements of efficacy were shown both in resuscitation knowledge and skill performance immediately after training. However, in current studies, the long-time retention of benefits is controversial, and these benefits may not transfer to the real-life situations.

Mapping the knowledge structure and trends of epilepsy genetics over the past decade: A co-word analysis based on medical subject headings terms.

INTRODUCTION: Over the past 10 years, epilepsy genetics has made dramatic progress. This study aimed to analyze the knowledge structure and the advancement of epilepsy genetics over the past decade based on co-word analysis of medical subject headings (MeSH) terms. METHODS: Scientific publications focusing on epilepsy genetics from the PubMed database (January 2009-December 2018) were retrieved. Bibliometric information was analyzed quantitatively using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) software. A knowledge social network analysis and publication trend based on the high-frequency MeSH terms was built using VOSviewer. RESULTS: According to the search strategy, a total of 5185 papers were included. Among all the extracted MeSH terms, 86 high-frequency MeSH terms were identified. Hot spots were clustered into 5 categories including: "ion channel diseases," "beyond ion channel diseases," "experimental research & epigenetics," "single nucleotide polymorphism & pharmacogenetics," and "genetic techniques". "Epilepsy," "mutation," and "seizures," were located at the center of the knowledge network. "Ion channel diseases" are typically in the most prominent position of epilepsy genetics research. "Beyond ion channel diseases" and "genetic techniques," however, have gradually grown into research cores and trends, such as "intellectual disability," "infantile spasms," "phenotype," "exome," " deoxyribonucleic acid (DNA) copy number variations," and "application of next-generation sequencing." While ion channel genes such as "SCN1A," "KCNQ2," "SCN2A," "SCN8A" accounted for nearly half of epilepsy genes in MeSH terms, a number of additional beyond ion channel genes like "CDKL5," "STXBP1," "PCDH19," "PRRT2," "LGI1," "ALDH7A1," "MECP2," "EPM2A," "ARX," "SLC2A1," and more were becoming increasingly popular. In contrast, gene therapies, treatment outcome, and genotype-phenotype correlations were still in their early stages of research. CONCLUSION: This co-word analysis provides an overview of epilepsy genetics research over the past decade. The 5 research categories display publication hot spots and trends in epilepsy genetics research which could consequently supply some direction for geneticists and epileptologists when launching new projects.

Role of toll-like receptor 4 in the regulation of the cell death pathway and neuroinflammation.

Septic brain injury is a severe disease of the central nervous system and involves alteration of the cell death pathway due to sepsis. Increasing evidence indicates that Toll-like receptor 4 (TLR4) plays a key role in the development of sepsis. Cell death is also thought to contribute to septic brain injury. However, the mechanism that regulates cell death pathways in response to TLR4 in neurons exposed to septic brain injury is unclear. Here, we established a rat model of septic brain injury to evaluate the effect of TLR4 inhibition on cell death pathways. Furthermore, primary neurons with and those without TLR4 inhibition were exposed to lipopolysaccharide (LPS). We found that septic brain injury induction by cecum ligation and puncture evoked autophagy, induced high-mobility group box-1(HMGB1) translocation and increased TLR4 expression. Inhibition of TLR4 also enhanced autophagy and increased nuclear HMGB1 levels in the sepsis-injured rat brain cortex. After LPS treatment in vitro, HMGB1 was released from neurons. This release of HMGB1 could be inhibited using a TLR4 inhibitor. Collectively, these results indicate that modulation of TLR4 may result in the regulation of neuron cell death pathways by regulating autophagy in cortical tissues. Thus, it may represent a potential therapeutic strategy for neuronal protection in septic brain injury.

Histone acetylation of oligodendrocytes protects against white matter injury induced by inflammation and hypoxia-ischemia through activation of BDNF-TrkB signaling pathway in neonatal rats.

The major pathological damage in encephalopathy of prematurity is white matter injury (WMI). Perinatal hypoxic-ischemia (HI) and inflammation are two major risk factors in the development of WMI. To study the cellular and molecular mechanisms of WMI, we set up a WMI model using lipopolysaccharide-sensitized HI injury in 2-day postnatal rats. Immunofluorescence staining was used to measure the expression of acetylated histone H3 (AH3) in oligodendrocytes, the target cells of WMI; the oligodendrocyte protein markers, NG2, O4, MBP, PLP, and MAG, were detected at different developmental stages. 5-bromo-2'-deoxyuridine (BrdU) was used to detect the proliferation of oligodendrocytes. We found that the expression of AH3 was markedly decreased in oligodendrocytes at 7 days after WMI. The differentiation and maturation of oligodendrocytes were inhibited in the WMI group. After inducing histone acetylation in oligodendrocytes by treatment with sodium butyrate, the inhibition of differentiation and maturation of oligodendrocytes was reversed. Furthermore, we found that these protective effects of histone acetylation were associated with the upregulation of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase B (TrkB). In conclusion, histone acetylation protects oligodendrocytes from WMI through activation of the BDNF-TrkB signaling pathway in immature brains.

Association between perinatal hypoxic-ischemia and periventricular leukomalacia in preterm infants: A systematic review and meta-analysis.

BACKGROUND: Although investigators have implicated hypoxic-ischemia (HI) as a potential cause of periventricular leukomalacia (PVL), the role of clinical risk factors or markers for HI in the development of PVL remains controversial. The aim of this study was to identify perinatal HI-related factors associated with PVL. METHOD: The PubMed, EMBASE, and Cochrane Library databases were searched. The last search was performed on January 2017. Summary effect estimates (pooled odds ratios [ORs]) were calculated for each risk factor using fixed or random effects models with tests for heterogeneity and publication bias. RESULTS: Fifteen studies with a total of 12,851 participants were included in this meta-analysis, and 14 potential risk factors were analyzed. The pooled results showed that mothers with oligohydramnios (OR, 1.55; 95% confidence interval [CI], 1.05 to 2.30), preterm infants with acidemia (OR, 1.87; 95% CI, 1.18 to 2.97), 1-minute Apgar score <7 (OR 2.69; 95% CI, 1.13 to 6.41), 5-minute Apgar score <7 (OR, 1.89; 95% CI, 1.39 to 2.56), apnea (OR, 1.76; 95% CI, 1.07 to 2.90), respiratory distress syndrome (OR, 1.46; 95% CI, 1.04 to 2.03), and seizures (OR, 4.60; 95% CI, 2.84 to 7.46) were associated with increased risk of PVL. CONCLUSION: This study identified perinatal HI-related risk factors for the development of PVL in preterm infants. Future large-scale prospective clinical studies are required to validate and extend these findings.

[Protective effect of histone acetylation against cortical injury in neonatal rats].

OBJECTIVE: To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats. METHODS: A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6.5%) for 90 minutes. The rats in the sham-operation group were intraperitoneally injected with normal saline and the right common carotid artery was only separated and exposed without ligation or hypoxic treatment. The rats in the sodium butyrate treatment group were intraperitoneally injected with sodium butyrate (300 mg/kg) immediately after establishment of the cortical injury model once a day for 7 days. Those in the sham-operation and the model groups were injected with the same volume of normal saline. At 7 days after establishment of the model, Western blot was used to measure the protein expression of histone H3 (HH3), acetylated histone H3 (AH3), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (BAX), cleaved caspase-3 (CC3), and brain-derived neurotrophic factor (BDNF). Immunofluorescence assay was used to measure the expression of 5-bromo-2'-deoxyuridine (BrdU) as the cortex cell proliferation index. RESULTS: The sodium butyrate treatment group had a significantly lower HH3/AH3 ratio than the model group (P<0.05), which suggested that the sodium butyrate treatment group had increased acetylation of HH3. Compared with the model group, the sodium butyrate treatment group had a significant increase in Bcl-2/Bax ratio, a significant reduction in CC3 expression, and a significant increase in BDNF expression (P<0.05). The sodium butyrate treatment group had a significant increase in the number of BrdU-positive cells in the cortex compared with the model group (P<0.05), and BrdU was mainly expressed in the neurons. CONCLUSIONS: Increased histone acetylation may protect neonatal rats against cortical injury by reducing apoptosis and promoting regeneration of neurons. The mechanism may be associated with increased expression of BDNF.

Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury.

High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.

Peripheral brain-derived neurotrophic factor in autism spectrum disorder: a systematic review and meta-analysis.

Brain-derived neurotrophic factor (BDNF) regulates neuronal survival and growth and promotes synaptic plasticity. Recently, researchers have begun to explore the relationship between peripheral BDNF levels and autism spectrum disorder (ASD), but the findings are inconsistent. We undertook the first systematic review and meta-analysis of studies examining peripheral BDNF levels in ASD compared with healthy controls. The PubMed, Embase, and Cochrane Library databases were searched for studies published before February 2016. Fourteen studies involving 2,707 participants and 1,131 incident cases were included. The meta-analysis provided evidence of higher peripheral BDNF levels in ASD compared with controls [standardized mean difference (SMD) = 0.63, 95% confidence interval (95% CI) = 0.18-1.08; P = 0.006]. Subgroup analyses revealed higher BDNF levels in ASD compared with controls for both serum [SMD = 0.58, 95% CI = 0.11-1.04; P = 0.02] and plasma [SMD = 1.27, 95% CI = 0.92-1.61; P < 0.001]. Studies of childhood yielded similar cumulative effect size [SMD = 0.78, 95% CI = 0.31-1.26; P = 0.001], while this was not true for the studies of adulthood [SMD = 0.04, 95% CI = -1.72-1.80; P = 0.97]. This meta-analysis suggests that peripheral BDNF levels are a potential biomarker of ASD.

Association between Asthma and Autism Spectrum Disorder: A Meta-Analysis.

OBJECTIVE: We conducted a meta-analysis to summarize the evidence from epidemiological studies of the association between asthma and autism spectrum disorder (ASD). METHODS: A literature search was conducted using PubMed, Embase, and Cochrane library for studies published before February 2nd, 2016. Observational studies investigating the association between asthma and ASD were included. A random effects model was used to calculate the pooled risk estimates for the outcome. Subgroup analysis was used to explore potential sources of heterogeneity and publication bias was estimated using Begg's and Egger's tests. RESULTS: Ten studies encompassing 175,406 participants and 8,809 cases of ASD were included in this meta-analysis. In the cross-sectional studies, the prevalence of asthma in ASD was 20.4%, while the prevalence of asthma in controls was 15.4% (P < 0.001). The pooled odds ratio (OR) for the prevalence of asthma in ASD in the cross-sectional studies was 1.26 (95% confidence interval (CI): 0.98-1.61) (P = 0.07), with moderate heterogeneity (I2 = 65.0%, P = 0.02) across studies. In the case-control studies, the pooled OR for the prevalence of asthma in ASD was 0.98 (95% CI: 0.68-1.43) (P = 0.94), and there was no evidence of an association between asthma and ASD. No evidence of significant publication bias on the association between asthma and ASD was found. CONCLUSIONS: In conclusion, the results of this meta-analysis do not suggest an association between asthma and ASD. Further prospective studies ascertaining the association between asthma and ASD are warranted.

Association Between Perinatal Hypoxic-Ischemic Conditions and Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder worldwide, but its etiology is still not fully understood. Previous studies have reported that perinatal hypoxic-ischemic conditions may be a potential cause of ADHD. METHODS: An online search of potential English studies published before September 2015 was conducted using the PsycINFO, EMBASE, Web of Science, and PubMed databases. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models. RESULTS: Ten studies were included, with 45 821 cases and 9 207 363 controls. The metaresults found that the following were associated with ADHD: preeclampsia (OR 1.31; 95% CI 1.26-1.37), an Apgar score <7 at 5 minutes (OR 1.31; 95% CI 1.12-1.54), breech/transverse presentations (OR 1.14; 95% CI 1.06-1.23), and a prolapsed/nuchal cord (OR 1.10; 95% CI 1.06-1.15). CONCLUSION: Our results support that perinatal hypoxia-ischemia may contribute to ADHD. However, more clinical studies are warranted.

Prenatal, Perinatal and Neonatal Risk Factors for Intellectual Disability: A Systemic Review and Meta-Analysis.

BACKGROUND: The etiology of non-genetic intellectual disability (ID) is not fully known, and we aimed to identify the prenatal, perinatal and neonatal risk factors for ID. METHOD: PubMed and Embase databases were searched for studies that examined the association between pre-, peri- and neonatal factors and ID risk (keywords "intellectual disability" or "mental retardation" or "ID" or "MR" in combination with "prenatal" or "pregnancy" or "obstetric" or "perinatal" or "neonatal". The last search was updated on September 15, 2015. Summary effect estimates (pooled odds ratios) were calculated for each risk factor using random effects models, with tests for heterogeneity and publication bias. RESULTS: Seventeen studies with 55,344 patients and 5,723,749 control individuals were eligible for inclusion in our analysis, and 16 potential risk factors were analyzed. Ten prenatal factors (advanced maternal age, maternal black race, low maternal education, third or more parity, maternal alcohol use, maternal tobacco use, maternal diabetes, maternal hypertension, maternal epilepsy and maternal asthma), one perinatal factor (preterm birth) and two neonatal factors (male sex and low birth weight) were significantly associated with increased risk of ID. CONCLUSION: This systemic review and meta-analysis provides a comprehensive evidence-based assessment of the risk factors for ID. Future studies are encouraged to focus on perinatal and neonatal risk factors and the combined effects of multiple factors.

Mapping the Knowledge Structure of Neonatal Hypoxic-Ischemic Encephalopathy Over the Past Decade: A Co-word Analysis Based on Keywords.

The aim of this study was to analyze the knowledge structure and report the evolution of hypoxic-ischemic encephalopathy research over the past decade based on co-word analysis. Scientific publications focusing on neonatal hypoxic-ischemic encephalopathy were searched from the Web of Science database (January 2005 to December 2014). The keywords from these articles were extracted, and a knowledge network based on these keywords was built using Ucinet6.212 and NetDraw2.084 software. A total of 1892 papers were included, and 39 high-frequency keywords were defined. "HIE" and "neonate" located at the center of the knowledge network. Etiology and pathogenesis, clinical manifestation, and therapy were researched more widely in the network than other aspects of hypoxic-ischemic encephalopathy. This co-word analysis provides an overview of neonatal hypoxic-ischemic encephalopathy research and suggests that the etiology, clinical manifestation, and therapy of hypoxic-ischemic encephalopathy have become research cores over the past decade.

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis.

Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis.

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case-control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case-control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05-1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01-1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07-1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04-1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.

The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population.

BACKGROUND: The associations between the polymorphisms in Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) gene and Graves' disease (GD) have been extensively investigated in Chinese population. However, the results were inconsistent. The objective of this study is to investigate the associations between the polymorphisms in CTLA-4 gene and the risk of GD by meta-analysis. METHODS: We searched Pubmed database, Medline (Ovid) database, CNKI database and Wanfang database, covering all studies until August 11, 2012. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. RESULTS: A total of 28 case-control studies concerning the most widely studied three polymorphisms [+49A/G(rs231775), -318C/T(rs5742909) and CT60(rs3087243)] for Chinese population in 21 publications were included. The results suggested that the G allele carriers (GG+GA) might have an increased risk of GD when compared with the AA homozygote carriers for the +49A/G polymorphism (GG+GA vs. AA: OR = 2.57, 95%CI = 1.87-3.52). However, as to the -318C/T polymorphism and CT60 polymorphism, the results indicated that the variant allele carriers might have decreased risks of GD when compared with the homozygote carriers (-318C/T: TT+TC vs. CC: OR = 0.78, 95%CI = 0.62-0.97; CT60: AA+AG vs. GG: OR = 0.64, 95%CI = 0.52-0.78). CONCLUSIONS: The current meta-analysis indicated that the polymorphisms in the CLTA-4 gene might be risk factors for GD in the Chinese population. In future, more large-scale case-control studies are needed to validate these results.

The association between the poly(A) polymorphism in the VDR gene and cancer risk: a meta-analysis.

The poly(A) polymorphism (L/S) in the VDR gene has been implicated in susceptibility of cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between the poly(A) polymorphism in the VDR gene and cancer risk by meta-analysis. We searched PubMed database, EMBASE database, CNKI database, and Wanfang database, covering all studies until January 22, 2013. Statistical analysis was performed by using the software Revman4.2 and STATA 10.0. A total 8,186 cancer cases and 8,685 controls in 19 case-control studies from 15 studies were identified for data analysis. The results suggested that the S allele carriers (SS+SL) did not have an increased or decreased risk of cancer when compared with the homozygote LL carriers (odds ratio (OR) =0.96, 95 % CI=0.87-1.06, P=0.43 for SS+SL vs. LL). In addition, in the subgroup analysis by ethnicity and cancer type, no significant association was found among Caucasians, African-Americans, prostate cancer, or breast cancer. This current meta-analysis suggested that the poly(A) polymorphism in the VDR gene may not contribute to the risk of cancer. Future studies are needed to validate our findings.

The association between the methionine/valine (M/V) polymorphism (rs1799990) in the PRNP gene and the risk of Alzheimer disease: an update by meta-analysis.

BACKGROUND: The M/V polymorphism in the PRNP gene has been extensively examined for the association to the risk of Alzheimer disease (AD); however, results from different studies have been inconsistent. The aim of this study is to evaluate the association between the M/V polymorphism in the PRNP gene and the risk of AD. METHODS: A meta-analysis was carried out to analyze the association between the M/V polymorphism in the PRNP gene and the risk of AD. RESULTS: A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis. The results indicated that the variant V allele carriers (VV+MV) had a 13% decreased risk of AD, when compared with the homozygote MM (VV+MV vs. MM: OR=0.87, 95% CI=0.79-0.96, P=0.004). In the subgroup analysis by ethnicity, significant decreased risks of AD were found in the Caucasian V allele carriers (OR=0.85, 95% CI=0.77-0.94, P=0.002), but not in Asian V allele carriers (OR=1.11, 95% CI=0.78-1.57, P=0.57). In the subgroup analysis by age of onset, significant decreased risks of AD were associated with V allele carriers in late-onset Alzheimer disease (OR=0.76, 95% CI=0.62-0.93, P=0.007) but not in early-onset Alzheimer disease (OR=0.86, 95% CI=0.70-1.06, P=0.17). CONCLUSIONS: Our results suggest that the M/V polymorphism in the PRNP gene contributes to the susceptibility of Alzheimer disease.

The -444A/C polymorphism in the LTC4S gene and the risk of asthma: a meta-analysis.

BACKGROUND AND AIMS: The -444A/C polymorphism in the leukotriene C4 synthase (LTC4S) gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study was to investigate the association between the -444A/C polymorphism in the LTC4S gene and asthma risk using meta-analysis. METHODS: We searched Pubmed, Embase, CNKI and Wanfang databases. Statistical analysis was performed using the software Revman4.2 and STATA10.0. RESULTS: A total of 3042 cases and 1902 controls in 13 case-control studies were included in the meta-analysis. The results indicated that the variant C allele carriers (CC + AC) did not have increased/decreased risk of asthma when compared with the homozygote AA (CC + AC vs. AA: OR = 1.13, 95% CI = 1.00-1.28, p = 0.06). In the subgroup analysis by age, ethnicity and aspirin sensitivity, significantly elevated risks were found only in Caucasians (OR = 1.21, 95% CI = 1.02-1.44, p = 0.03) and aspirin-tolerant populations (OR = 1.36, 95% CI = 1.12-1.65, p = 0.002) but not in other subgroups. CONCLUSIONS: This meta-analysis suggested that the -444A/C polymorphism in the LTC4S gene would be a risk factor for asthma in Caucasians and aspirin-tolerant populations. Future studies are needed to validate our results.