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INTRODUCTION Although numerous studies have suggested that lifestyle-related factors are associated with chronic diseases and preventable deaths, limited evidence is available for the Chinese population. METHODS This study established a prospective cohort of >360,000 residents on the basis of the Yinzhou Health Information System in China during 2004-2017 and calculated the combined effects of lifestyle-related factors, including BMI, smoking, alcohol consumption, and physical activity, using a points system. A Cox regression model estimated the combined effects of lifestyle-related factors on total mortality, and a competing risk model estimated the combined effects on cancer and cardiovascular disease mortality. All data analyses were conducted in 2018‒2019. RESULTS During 3,755,879 person-years of follow-up, 11,791 deaths were identified, including 4,983 from cancer and 3,143 from cardiovascular disease. Having a standard BMI, never smoking, never drinking, and engaging in physical activity more than 4 times per week had protective effects on total mortality. Overall, the risk of total and cause-specific mortality increased with the increment of risk score. Compared with subjects in the lowest quartile, the risk of total and cause-specific mortality peaked among individuals in the fourth quartile (total mortality: hazard ratio=1.87, 95% CI=1.77, 1.98; cancer mortality: hazard ratio=2.05, 95% CI=1.87, 2.25; cardiovascular disease mortality: hazard ratio=1.51, 95% CI=1.35, 1.68). Sensitivity analyses excluding individuals with follow-up

Increasing single nucleotide polymorphisms (SNPs) have been identified to be associated with colorectal cancer (CRC). We aimed to investigate whether genetic risk scores (GRS) that aggregate information from multiple genetic variants can predict the risk of CRC in a Chinese population. Fifty candidate SNPs were selected to explore the associations with CRC in a discovery sample with 1002 CRC cases and 999 healthy controls. We modeled the significant SNPs identified by the case-control study as a multilocus weighted GRS and estimated the association of GRS with CRC. Furthermore, 300 pairs of cases and controls were included as a validation sample to confirm the finding. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive power of GRS in CRC. A total of seven SNPs were found to increase the risk of CRC, and two SNPs were found to be negatively associated with CRC in the discovery sample. Relative to participants with the lowest quartile of GRS, those with the highest quartile had a 2.64-fold (95% CI: 1.99-3.51) higher risk for CRC. For every 0.1 point of GRS increase, the risk of CRC increase by 11% (95% CI: 8-14%). AUROC for GRS alone were 0.59 (95% CI: 0.57-0.62) and 0.52 (95% CI: 0.46-0.58) in the discovery and validation sample, respectively. AUROC increased to 0.62 (95% CI: 0.59-0.64) and 0.71 (95% CI: 0.65-0.76) by combining environmental risk factors. Our findings support an association between GRS and risk of CRC, which provides evidence of improved prediction model for CRC in China.

Background: RP11-108K3.2 was recently identified as a novel long non-coding RNA (lncRNA) transcript, and several single nucleotide polymorphisms (SNPs) have been identified in its coding region. This study aimed to explore the associations of tagSNPs in RP11-108K3.2 with the risk of colorectal cancer and their effects on its expression. Methods: A total of 821 colorectal cancer cases and 857 healthy controls were enrolled into this two-stage case-control study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. Six tagSNPs were genotyped by using Sequenom MassARRAY platform. A total of 71 additional colorectal cancer cases were recruited, of which the genotypes of potential polymorphisms and the RP11-108K3.2 expression levels were determined. Results: In the discovery set, only the rs2470151 C/T polymorphism was found to have a promising association with the risk of colorectal cancer, and this polymorphism was further replicated in the validation set with a significantly decreased risk of colorectal cancer (adjusted odds ratio 0.73; 95% confidence interval 0.55, 0.97). Combined discovery set and validation set together, this negative association was found both in the heterozygote codominant model and the dominant model. Furthermore, colorectal cancer patients carrying rs2470151 CT/TT genotypes had a marginally lower RNA expression of RP11-108K3.2 than those carrying the CC genotype. Stratified analyses showed the association between rs2470151 and the risk of colorectal cancer were influenced by family history of cancer, smoking, alcohol consumption, and tea drinking. Conclusions: These findings suggest that RP11-108K3.2 rs2470151 had a significant association with the risk of colorectal cancer; this may help to predict the susceptibility of colorectal cancer in Chinese populations.

BackgroundWe conducted this study to investigate the prevalence of myopia among school students in Ningbo and to explore the associations between reading and writing postures and myopia.MethodsA population-based and cross-sectional study was conducted, and 3,256 school students aged 8–19 years were recruited. Each enrolled subject was assessed for uncorrected distance visual acuity (UDVA) using a standard logarithmic visual acuity E-chart and a non-cycloplegic autorefraction examination. Self-administered questionnaires were used to investigate myopia-related reading and writing postures and behavioral habits among school students.ResultsThe prevalence of myopia among primary school, middle school, and high school students was 61.49, 81.43, and 89.72%, respectively. Regarding the associations between reading and writing postures and myopia, we identified that a reading distance >33 cm is a protective factor for myopia in female students [odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.15–0.64], in both primary school (OR = 0.55, 95% CI = 0.30–0.99) and middle school (OR = 0.37, 95% CI = 0.15–0.90).ConclusionsA reading distance >33 cm can be used as an additional measure to prevent and control myopia. Proper postural measures for reading and writing may have educational and public health benefits.

Purpose: We conducted this study to examine the prevalence of myopia among school students in Ningbo, and to explore the associations between reading and writing posture and myopia.Methods: A population-based and cross-sectional investigation was performed and 3256 school students aged 8 to 19 years old were recruited. Each enrolled subject underwent uncorrected distance visual acuity (UDVA) assessment using a standard logarithmic visual acuity E chart and non-cycloplegic autorefraction examination. Self-administered questionnaires were used to investigate myopia-related reading and writing posture and behavior habits.Results: Myopia prevalence of primary school students, middle school students and high school students were 61.49%, 81.43% and 89.72%, respectively. In the associations between reading and writing posture and myopia, we identified keeping the distance between the eyes and the book could be the protective factor in female students, and in both primary school students and middle school students.Conclusions: Keeping appropriate distance between the eyes and the book may be good for myopia prevention and control. We hope this work will bring educational and public health benefits to form appropriate reading and writing posture.

Backgrounds Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. Methods We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. Results A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. Conclusions The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.

Objective. To assess the association between the expression level of miR-16 and prognosis of solid cancer patients by meta-analysis and bioinformatic analysis. Methods. PubMed, Web of Science, and Embase databases were searched until October 31, 2019, to identify eligible studies reporting the association of the miR-16 status with the prognosis of solid cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled, and a heterogeneity test was conducted. Sensitivity analysis and a publication bias test were also carried out. Furthermore, the miRpower database was used to validate the association. Results. Thirteen articles with 2303 solid cancer patients were included in the meta-analysis. Solid cancer patients with low expression level of miR-16 had shorter survival time (I2=84.0%, HR=1.47, 95% CI: 1.13-1.91, P=0.004). In the subgroup analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (I2=33.3%, HR=1.24, 95% CI: 1.06-1.45, P=0.008). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg’s test and Egger’s test revealed no publication bias in the meta-analysis. In bioinformatic analysis, the significant association between miR-16 level and prognosis of patients with reproductive system cancers was further confirmed (HR=1.21, 95% CI: 1.03-1.42, P=0.017). Conclusion. Low expression level of miR-16 is an indicator for poor prognosis of solid cancer patients, particularly in reproductive system cancers.

Objective: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. Methods: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. Results: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P

As a common antagonist of Wnt/β-catenin signaling, Wnt inhibitory factor 1 (WIF1) plays an important role in the tumor progression. The aim of our meta-analysis was to summarize the diagnostic value of WIF1 methylation in colorectal cancer (CRC). Eligible studies were retrieved by a systemic search among PubMed, Embase, CNKI, and Wanfang literature databases. The diagnostic value of WIF1 methylation for CRC was assessed by the summary receiver operating characteristics (SROC) test. Our meta-analysis of 12 studies between 1420 CRC samples and 946 control samples showed that WIF1 hypermethylation was significantly associated with CRC (P < 0.001, OR = 30.10, 95% CI = 19.48-46.50). WIF1 hypermethylation, as a diagnostic biomarker for CRC, has a pooled sensitivity of 0.40 (95% CI: 0.37-0.42), a pooled specificity of 0.95 (95% CI: 0.93-0.96), a pooled positive-likelihood ratio (PLR) of 8.65 (95% CI, 4.47-16.73), and a pooled negative-likelihood ratio (NLR) of 0.41 (95% CI, 0.30-0.55), a diagnostic odds ratio (DOR) of 26.86 (95% CI: 15.73-45.89), and an area under the curve (AUC) of 0.9115. In conclusion, our study established that WIF1 hypermethylation might be a promising diagnostic biomarker for CRC.

The prognostic value of long interspersed nucleotide element-1 (LINE-1) methylation in patients with colorectal cancer (CRC) remains uncertain. We have therefore performed a meta-analysis to elucidate this issue.The PubMed and Web of Science databases were searched for studies published up to 30 June 2016 which reported on an association between LINE-1 methylation and overall survival (OS), disease-free survival (DFS), or cancer-specific survival (CSS) among CRC patients. The reference lists of the identified studies were also analyzed to identify additional eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects or the random-effects model. Stratification analysis and meta-regression analysis were performed to detect the source of heterogeneity. Analyses of sensitivity and publication bias were also carried out.Thirteen independent studies involving 3620 CRC patients were recruited to the meta-analysis. LINE-1 hypomethylation was found to be significantly associated with shorter OS (HR 2.92, 95% CI 2.20-3.88, p 0.001) and DFS (HR 2.18, 95% CI 1.46-3.27, p 0.001), as well as unfavorable CSS (HR 1.96, 95% CI 1.35-2.85, p 0.001). No heterogeneity was found among the studies evaluating the associations between LINE-1 hypomethylation and OS or DFS, with the exception being CSS. Moreover, meta-regression analysis suggested that one of the contributors to between-study heterogeneity on the association between LINE-1 methylation and CSS was statistical methodology. The subgroup analysis suggested that the association in studies using the Cox model statistical method (HR 2.76, 95% CI 1.90-4.01, p 0.001) was stronger than that in studies using the Log-rank test (HR 1.41, 95% CI 1.07-1.87, p = 0.015).The results of this meta-analysis suggest that LINE-1 methylation is significantly associated with the survival of CRC patients and that it could be a predictive factor for CRC prognosis.

// Cheng Zhang 1 , Jinyun Li 2 , Tao Huang 2 , Shiwei Duan 2 , Dongjun Dai 2 , Danjie Jiang 2 , Xinbing Sui 3 , Da Li 3 , Yidan Chen 1 , Fei Ding 1 , Changxin Huang 1 , Gongying Chen 1 , Kaifeng Wang 1 1 Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China 2 Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China 3 Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China Correspondence to: Kaifeng Wang, email: wangkf2000@163.com Gongying Chen, email: chengongying@hotmail.com Keywords: meta-analysis, DNA methylation, biomarker, hepatocellular carcinoma Received: May 03, 2016 Accepted: November 01, 2016 Published: November 08, 2016 ABSTRACT DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC. Subgroup meta-analysis by geographical populations showed that six genes (carcinoma tissues vs adjacent tissues) and four genes (carcinoma tissues vs normal tissues) were significantly hypermethylated in HCC. Our meta-analysis identified the correlations between a number of aberrant methylated genes ( p16 , RASSF1A , GSTP1 , p14 , CDH1 , APC , RUNX3 , SOCS1 , p15 , MGMT , SFRP1 , WIF1 , PRDM2 , DAPK1 , RARβ , hMLH1 , p73 , DLC1 , p53 , SPINT2 , OPCML and WT1 ) and HCC. Aberrant DNA methylation might become useful biomarkers for the prediction and diagnosis of HCC.

Aberrant promoter DNA methylation is a major mechanism of leukemogenesis in hematologic malignancies, including acute myeloid leukemia (AML). However, the association between promoter methylation with chemotherapeutic outcomes remains unknown. In the present study, bone marrow samples were collected prior to and following chemotherapy in 30 AML patients. Methylation-specific polymerase chain reaction technology was used to examine the promoter methylation status of adenomatous polyposis col 2 (APC2) and cytochrome P450 family 1 subfamily B polypeptide 1 (CYP1B1). The results revealed no change in the methylation status of the APC2 promoter in patients following various chemotherapy regimens. However, the methylation status of the CYP1B1 promoter changed in response to 6 different chemotherapy regimens. AML patients of the M3 subtype displayed an induction of the CYP1B1 promoter methylation levels more frequently (57.1%) than patients affected by the other subtypes (M1: 33.3%; M2: 12.5%; M4: 16.7%; M5: 0% and M6: 0%). In addition, a higher frequency of male patients (4/13) exhibited modulation of the CYP1B1 promoter methylation status compared with female patients (3/17). Furthermore, of five AML patients with a poor prognosis, two exhibited changes leading to CYP1B1 hypomethylation and two leading to CYP1B1 hypermethylation. By contrast, three other patients exhibited hypermethylation changes along with remission. This may be explained by the different chemotherapy regimens used to treat these patients or by other unknown factors. The present study revealed that CYP1B1 promoter methylation was induced during chemotherapy, whereas the APC2 promoter remained hemimethylated. Furthermore, the changes in CYP1B1 methylation were dependent on the AML subtypes and the gender of the patients.

Background The association between Alu methylation and risk of cancer remains uncertain. This meta-analysis was conducted to elucidate this issue. Materials and Methods PubMed and Web of Science up to December 31, 2018, and the reference lists of studies, as well as those presented in relevant meta-analyses and reviews were systematically searched. Standardized mean difference (SMD) in Alu methylation level between cases and controls were pooled using random effects model and assessed heterogeneity between strata by stratified factors using meta-regression model. Sensitivity analysis and publication bias test were also conducted. Results Twenty-five articles, including 2719 cases and 3018 controls were included in the meta-analysis. The significant difference in Alu methylation level between cancer cases and controls was greater in tissue (SMD = −1.89, 95% CI: −2.72, −1.05) than blood (SMD = −0.46, 95% CI: −0.82, −0.09), and heterogeneity was found in materials (P = 0.038). In tissue samples, Alu hypomethylation was found in carcinoma (SMD = −2.50, 95% CI: −3.51, −1.48), while not in non-carcinoma. The inverse associations were consistently found in subgroups stratified by data sources and quality score in tissue samples, and publication year was considered to be the potential source of between-study heterogeneity. Moreover, reduced Alu methylation level was found in the European subgroup, detection method of SIRPH and COBRA, and original data source in blood samples. Conclusions Alu hypomethylation was associated with increased risk of cancer, which could be a potential biomarker for cancer.

Supplemental material, Supplementary_Table_1 for Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression by Danjie Jiang, Mingjuan Jin, Ding Ye, Yingjun Li, Fangyuan Jing, Xiaocong Zhang, Qilong Li and Kun Chen in The International Journal of Biological Markers

Table S3. Results of ROC curve analysis between CRC tissues and adjacent normal tissues. (DOCX 12 kb)

Table S2. A list of differentially hypermethylated and expressed genes identified by both EPIC array and TCGA database. (DOCX 173 kb)

Table S1. Pyrosequencing methylation assay Primers. (DOCX 13 kb)

Cyclin dependent kinase inhibitor 2B (CDKN2B) encodes a cyclin-dependent kinase inhibitor that may enhance the formation of atherosclerotic plaques. The aim of the present study was to investigate the contribution of CDKN2B promoter methylation on the risk of coronary heart disease (CHD). The present results indicated a significant association between increased CDKN2B methylation and the risk of CHD (adjusted P=0.043). A breakdown analysis according to sex demonstrated that CDKN2B methylation was significantly associated with the risk of CHD in women (adjusted P=0.010), but not in men. A further breakdown analysis by age indicated a significant association of CHD in the women >60 years (P=0.024). Luciferase reporter gene assay results indicated that the CDKN2B promoter fragment significantly enhanced luciferase activity (P

Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer's disease (AD). The goal of the present study was to determine whether dopamine receptor D4 (DRD4) promoter methylation is associated with AD. In the current study, the methylation levels of the DRD4 promoter were measured in 46 AD patients and 61 controls using bisulfite pyrosequencing technology. The results of the present study demonstrated that DRD4 promoter methylation was significantly higher in AD patients than in controls. A further breakdown analysis by gender revealed that there was a significant association of DRD4 promoter methylation with AD in males (23 patients and 45 controls). In conclusion, the results of the present study demonstrated that elevated DRD4 promoter methylation was associated with AD risk in males.

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, I2=78%). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/ adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, I2=55%). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with β-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08–3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.

Promoter DNA methylation may reflect the interaction between genetic backgrounds and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). Calcium/calmodulin-dependent protein kinase 1D (CAMK1D), cryptochrome 2 (CRY2) and calmodulin 2 (CALM2) genes have been identified to be associated with a risk of T2D. Therefore, the aim of the present study was to investigate the contribution of promoter DNA methylation of these genes to the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of the CpG dinucleotides within the CAMK1D, CRY2 and CALM2 gene promoters were measured in 48 patients with T2D and 48 age- and gender-matched healthy controls. The results demonstrated that the promoters of these three genes were hypomethylated in the peripheral blood of all the subjects, and DNA methylation of these three genes did not contribute to the risk of T2D.

Objectives. Glucokinase encoded byGCKis a key enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Variants ofGCKgene were shown to be associated with type 2 diabetes (T2D) and coronary heart disease (CHD). The goal of this study was to investigate the contribution ofGCKgene-body methylation to the risk of CHD.Design and Methods. 36 patients (18 males and 18 females) and 36 age- and sex-matched controls were collected for the current methylation research. DNA methylation level of the CpG island (CGI) region on theGCKgene-body was measured through the sodium bisulfite DNA conversion and pyrosequencing technology.Results.Our results indicated that CHD cases have a much lower methylation level (49.77 ± 6.43%) compared with controls (54.47 ± 7.65%,P=0.018). In addition,GCKgene-body methylation was found to be positively associated with aging in controls (r=0.443,P=0.010).Conclusions. Our study indicated that the hypomethylation ofGCKgene-body was significantly associated with the risk of CHD. Aging correlates with an elevation ofGCKmethylation in healthy controls.

MiRNAs are potent regulators of gene expression, and most miRNAs have from several to several thousands of gene targets. Validating the numerous gene targets of a given miRNA remains challenging despite the existence of various tools and databases that predict candidate gene-miRNA pairs. In the present study, we present a high-throughput but flexible method that applies a PCR-based application to simulate the binding of miRNAs to their gene targets. Using hsa-miR-377 as an illustrative example, our method was able to identify 13 potential targets of hsa-miR-377. Moreover, our results include 2 genes (SOD2 and PPM1A) that have already been verified as targets of hsa-miR-377. Our method may provide an alternative way of identifying the gene targets of miRNAs for future research.

Previous studies have shown that apolipoprotein A5 (APOA5) gene variants are genetic determinants of the concentration of triglycerides, which are a known risk factor for coronary heart disease (CHD). Using the standardized coronary angiography method, 290 CHD patients and 198 non-CHD controls were recruited from Ningbo Lihuili Hospital. In addition, 331 unrelated healthy volunteers were recruited as healthy controls from Ningbo Ximen Community residents. Three variants of the APOA5 gene, S19W, -1131T>C and 553G>T, were analyzed for their association with CHD. Under a dominant inheritance model, -1131CT>C was shown to be a CHD risk factor (P=0.030; OR, 1.422; 95% CI, 1.036–1.952). The single nucleotide polymorphism, 553G>T, was found to correlate with the severity of CHD in males (P=0.032). Meta-analysis showed that -1131T>C was significantly associated with CHD (PT. In the present case-control study, APOA5 gene variants were not found to correlate with the risk of CHD in the populations studied; however, -1131CT>C was shown to be a CHD risk factor under a dominant inheritance model. Meta-analysis showed a significant contribution of -1131T>C to the risk of CHD, implying an ethnic difference in APOA5 gene variants.

Previous genome-wide association studies (GWAS) have revealed seven single nucleotide polymorphisms (SNPs) that affect lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity or levels in American and European individuals. A total of 290 coronary heart disease (CHD) patients, 198 non-CHD patients and 331 unrelated healthy volunteers were recruited for the present case-control study of Han Chinese. Four SNPs (rs964184 of ZNF259, rs7528419 of CELSR2 and rs7756935 and rs1805017 of PLA2G7) were shown to be significantly associated with CHD. The rs964184-G allele of the ZNF259 gene was identified as a risk factor of CHD in females (odds ratio (OR) =1.49, 95% confidence interval (CI) =1.00-2.22, P=0.05). The rs7528419-G allele of the CELSR2 gene was protective against CHD in males (OR=0.48, 95% CI=0.25-0.93, P=0.04). The other two alleles (rs7756935-C and rs1805017-A) of the PLA2G7 gene acted as protective factors against CHD in females (rs7756935-C: OR=0.59, 95% CI=0.35-1.00, P=0.05; rs1805017-A: OR=0.51, 95% CI=0.28-0.93, P=0.03). Moreover, rs1805017 of the PLA2G7 gene was associated with the severity of CHD only in females (r(2)=0.02, P=0.04). We identified four Lp-PLA(2)-associated SNPs significantly associated with CHD in a Han Chinese population. Specifically, rs7528419 was protective factor against CHD in males, while the other two SNPs (rs7756935 and rs1805017 of the PLA2G7 gene) were protective factors against CHD in females and rs964184 of the ZNF259 gene was regarded as a risk factor for CHD in females.

PPARD encodes peroxisome proliferator-activated re-ceptor delta, which has been shown to play an important role in control-ling lipid metabolism and atherosclerosis. In this case-control study, we explored the relationship between PPARD rs2016520 polymorphism and coronary heart disease (CHD) in a Han Chinese population. A to-tal of 657 CHD cases and 640 controls were included in the associa-tion study. rs2016520 polymorphism genotyping was performed using the melting temperature-shift polymerase chain reaction method. The PPARD rs2016520-G allele reduced CHD risk by 17.9% (χ(2) = 5.061, P = 0.025, OR = 0.821, 95%CI = 0.692-0.975). Furthermore, a signifi-cant difference in CHD risk was observed for the PPARD rs2016520 polymorphism in the dominant model (AG + GG vs AA: χ(2) = 4.751, degrees of freedom (df) = 1, P = 0.029, OR = 0.784, 95%CI = 0.631- 0.976). Analysis by age suggested that the G-allele decreased CHD risk by 14.8% in ages greater than 65 years (χ(2) = 4.446, P = 0.035, OR = 0.852, 95%CI = 0.684-1.060). In contrast, meta-analysis of PPARD rs2016520 among 3732 cases and 5042 controls revealed no associa-tion between PPARD rs2016520 and CHD (P = 0.19). We found that the PPARD rs2016520-GG genotype decreased CHD risk in a Han Chinese population. Moreover, we found an association between serum high-density lipoprotein cholesterol level and PPARD rs2016520 in senior individuals aged ≥ 65 years. The meta-analysis revealed no association between PPARD rs2016520 and CHD, suggesting ethnic differences in the association between the PPARD locus and CHD.

The O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the MGMT promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone marrow specimens was determined by methylation-specific polymerase chain reaction. The results indicated that the methylation status of the MGMT promoter was influenced by different chemotherapeutic regimens. The MGMT methylation status of M4 patients (3 out of 6) were more chemosensitive, compared with that of patients with other AML subtypes (M1, 1 out of 3; M2, 0 out of 8; M3, 3 out of 7; M5, 0 out of 3; and M6, 1 out of 3). Age-based analysis revealed that the group aged ≤60 years (7 out of 24 patients) exhibited more methylation changes than patients aged >60 years (1 out of 6). Male patients (4 out of 13) were more susceptible to chemotherapy-induced methylation changes than female patients (4 out of 17). Thus, the methylation status of the MGMT promoter may serve as a potential biomarker to predict the therapeutic outcomes in male AML patients. However, further studies in larger sample sets are required to confirm the present findings.

Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. Methods We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. Results Significant differences were observed between CHD cases and controls at the level of both genotype (χ2 = 8.964, df = 2, P = 0.011) and allele (χ2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089–1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088–1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). Conclusion Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.

Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated. A total of 4,325 leukemia patients and 2,010 controls from 94 studies on 53 genes were included in this meta-analysis, and 47 genes were found to be aberrantly methylated in leukemia patients. A further subgroup meta-analysis by leukemia subtype demonstrated that hypermethylation of 5 genes, namely cyclin-dependent kinase (CDKN)2A, DNA-binding protein inhibitor-4, CDKN2B, glioma pathogenesis-related protein 1 and p73, contributed to the risk of various subtypes of leukemia. In addition, a strong association between CDKN2A and leukemia was identified in Chinese (P

The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p = 0.002, allele: p = 0.002, odd ratio (OR) = 1.57, 95% confidential interval (CI) = 1.18–2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females (χ2 = 10.29, p = 0.003, OR = 2.14, 95% CI = 1.31–2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: χ2 = 14.64, degrees of freedom (df) = 2, p = 0.0002, allele: χ2 = 11.31, df = 1, p = 0.0008, OR = 1.87, 95% CI = 1.30–2.70). Similar observation was also found in males younger than 65 years (genotype: χ2 = 8.63, df = 2, p = 0.04, allele: χ2 = 7.55, df = 1, p = 0.006, OR = 1.45, 95% CI = 1.11–1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p &lt, 0.0001, OR = 1.27, 95% CI = 1.22–1.31).

Parkinson's disease (PD) is a neurodegenerative movement d'isorder that affects ~2% of the population aged ≥65 years. NAD(P)H-quinone oxidoreductase 1 (NQO1) and tumor necrosis factor-α (TNF-α) are two important factors in the generation of oxidative stress in PD. The aim of the present study was to assess the association of NQO1 and tumor necrosis factor (TNF) polymorphisms with PD. A meta-analysis was performed that included data from 15 studies comprising 2,858 patients and 2,907 healthy controls. The results showed that TNF-1031 (rs1799964) was significantly associated with PD in the recessive (P=0.0005; odds ratio (OR), 3.19; 95% confidence interval (CI), 1.66‑6.13) and additive models (P=0.0006; OR, 3.15; 95% CI, 1.63-3.51). However, there was no significant association in NQO1 C609T (rs1800566) and TNF-308 (rs1800629) with PD. To the best of our knowledge, the present study is the first meta-analysis of NQO1 and TNF polymorphisms with PD demonstrating that TNF-1031 polymorphism may be a risk factor for PD under either the recessive or additive models. However, the meta-analyses did not support the involvement of NQO1 C609T and TNF-308 in the risk of PD.

Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous cancer that has become the sixth leading cause of mortality in both the developed and developing countries. Accumulating evidence showed a number of genes with aberrant DNA methylation in the pathogenesis of PCa. Here, we conducted a systematic meta-analysis to evaluate the contribution of aberrantly methylated genes to the risk of PCa. Relevant methylation studies were retrieved from PubMed and Wanfang literature databases. In the meta-analysis, Mantel-Haenszel odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each methylation event under appropriate models. A total of 594 publications were initially retrieved from PubMed and Wanfang literature database. After a three-step filtration, we harvested 39 case-control articles investigating the role of gene methylation in the prediction of PCa risk. Among the 31 genes involved, 24 genes were shown to be significantly hypermethylated in the PCa patients. Our meta-analyses identified strong associations of four aberrantly methylated genes (GSTP1, RASSF1, p16, and RARB) with PCa. Further research is needed to strengthen our findings in the future.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that affects ~2% of the global population aged ≥65 years. Grb10-interacting GYF protein-2 (GIGYF2) can influence the development of PD through the regulation of insulin-like growth factor-1. The aim of the present meta-analysis study was to establish the contribution of GIGYF2 polymorphisms to PD. The study was conducted based on nine eligible studies consisting of 7,246 PD patients and 7,544 healthy controls. The results indicated that the GIGYF2 C.3630A>G polymorphism increased the risk of PD by 37% [P=0.008; odds ratio (OR), 1.37; 95% confidence interval (CI), 1.08–1.73] and that the GIGYF2 C.167G>A polymorphism was significantly associated with PD (P=0.003; OR, 3.67; 95% CI, 1.56–8.68). The meta-analyses of the other five GIGYF2 polymorphisms (C.1378C>A, C.1554G>A, C.2940A>G, C.1370C>A and C.3651G>A) did not reveal any significant associations. The present meta-analyses of the GIGYF2 genetic polymorphisms may provide a comprehensive overview of this PD candidate gene for future studies.

Schizophrenia (SCZ) is a severe complex psychi- atric disorder that generates problems for the associated family and society and causes disability with regards to work for patients. The aim of the present study was to assess the contri- bution of 10 genetic polymorphisms to SCZ susceptibility. Meta-analyses were conducted using the data without a limita- tion for time or language. A total of 27 studies with 7 genes and 10 polymorphisms were selected for the meta-analyses. Two polymorphisms were found to be significantly associ - ated with SCZ. SNAP25 rs3746544 was shown to increase the SCZ risk by 18% (P=0.01; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.05-1.34) and GRIK3 rs6691840 was found to increase the risk by 30% (P=0.008; OR, 1.30; 95% CI, 1.07‑1.58). Significant results were found under the dominant (P=0.001; OR, 1.36; 95% CI, 1.13-1.65) and additive (P=0.02; OR, 1.45; 95% CI, 1.06-1.98) model for the SNAP25 rs3746544 polymorphism and under the additive model for the GRIK3 rs6691840 polymorphism (P=0.03; OR, 1.73; 95% CI, 1.04‑2.85). There were no significant results observed for the other eight polymorphisms, which were CCKAR rs1800857, CHRNA7 rs904952, CHRNA7 rs6494223, CHRNA7 rs2337506, DBH Ins>Del, FEZ1 rs559668, FEZ1 rs597570 and GCLM rs2301022. In conclusion, the present meta-analyses indicated that the SNAP25 rs3746544 and GRIK3 rs6691840 polymorphisms were risk factors of SCZ, which may provide valuable information for the clinical diagnosis of SCZ.

Background Accumulating evidence supports a role of DNA methylation in the pathogenesis of leukemia. The aim of our study was to evaluate the potential genes with aberrant DNA methylation in the prediction of leukemia risk by a comprehensive meta-analysis of the published data. Methods A series of meta-analyses were done among the eligible studies that were harvested after a careful filtration of the searching results from PubMed literature database. Mantel-Haenszel odds ratios and 95% confidence intervals were computed for each methylation event assuming the appropriate model. Results A total of 535 publications were initially retrieved from PubMed literature database. After a three-step filtration, we harvested 41 case-control articles that studied the role of gene methylation in the prediction of leukemia risk. Among the involving 30 genes, 20 genes were shown to be aberrantly methylated in the leukemia patients. A further subgroup meta-analysis by subtype of leukemia showed that CDKN2A, CDKN2B, ID4 genes were significantly hypermethylated in acute myeloid leukemia. Conclusions Our meta-analyses identified strong associations between a number of genes with aberrant DNA methylation and leukemia. Further studies should be required to confirm the results in the future.

The current study was the first one to reveal the contribution of DRD3 methylation to the risk of different (SCZ) subtypes. This study comprised a total of 30 paranoid (15 males and 15 females) and 29 undifferentiated (15 males and 14 females) SCZ patients and 26 age- and gender-matched controls. Our results showed a significant association of CpG2 with SCZ. A breakdown analysis by gender showed that CpG2 and CpG3 methylation were significantly higher in male patients than male controls, and that CpG5 methylation was significantly higher in female patients than female controls. A further breakdown analysis by both gender and SCZ subtype showed that CpG2 and CpG3 methylation were significantly higher in male paranoid SCZ and male undifferentiated SCZ than male controls. In contrast, CpG2 and CpG3 methylation were significantly lower in female undifferentiated SCZ than female controls. Additionally, CpG5 methylation was significantly higher in female paranoid SCZ than female controls. In conclusion, our findings supported that DRD3 gene body hypermethylation was significantly associated with the risk of SCZ. Future study is needed to clarify the mechanisms by which DRD3 gene body hypermethylation contributes to the risk of SCZ.

Aim HFE gene variants can cause hereditary hemochromatosis (HH) that often comes along with an increased risk of coronary heart disease (CHD). The goal of our study is to assess the contribution of four HFE gene variants to the risk of CHD. Methods and results We conducted four meta-analyses of the studies examining the association between four HFE gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. Results Meta-analyses showed that HFE rs1799945-G allele was associated with a 6% increased risk of CHD (P = 0.02, odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01–1.11). However, no association between the other three HFE gene variants (rs1800562, rs1800730, and rs9366637) and CHD risk was observed by the meta-analyses (all P values > 0.05). In addition, the results of our case–control study indicated that rs1800562 and rs1800730 were monomorphic, and that rs1799945 and rs9366637 were not associated with CHD in Han Chinese. Conclusions Our meta-analysis suggested that a significant association existed between rs1799945 mutation and CHD, although this mutation was rare in Han Chinese.