Search

The aim of our study was to perform a comprehensive analysis of the gene expression, copy number variation (CNV) and mutation of key mitophagy genes in the progression and prognosis of lung adenocarcinoma (LUAD). We obtained the data from The Cancer Genome Atlas (TCGA). Clustering analysis was performed to stratify the mitophagy related groups. The least absolute shrinkage and selection operator (LASSO) based cox model was used to select hub survival genes. An independent validation cohort was retrieved from Gene Expression Omnibus database. We found 24 out of 27 mitophagy genes were aberrantly expressed between tumor and normal samples. CNV gains were associated with higher expression of mitophagy genes in 23 of 27 mitophagy genes. The clustering analysis identified high and low risk mitophagy groups with distinct survival differences. The high risk mitophagy groups had higher tumor mutation burden, stemness phenotype, total CNVs and lower CD4+ T cells infiltration. Drugs targeted to high risk mitophagy groups were identified including the PI3K/AKT/mTOR inhibitor, HDAC inhibitor and chemotherapy agents such as cisplatin and gemcitabine. In addition, the differentially expressed genes (DEGs) were identified between mitophagy groups. Further univariate Cox analysis of each DEG and subsequent LASSO-based Cox model revealed a mitophagy-related prognostic signature. The risk score model of this signature showed a strong ability to predict the overall survival of LUAD patients in training and validation datasets. In conclusion, the mitophagy genes played an important role in the progression and prognosis of LUAD, which might provide useful information for the treatment of LUAD.

Hepatocellular carcinoma (HCC) is the most common liver malignancy that can be developed from hepatitis B and cirrhosis. Many pathophysiological alterations, including hepatitis B virus (HBV) DNA integration, oxidative stress, cytokine release, telomerase homeostasis, mitochondrial damage, epigenetic modification, and tumor microenvironment, are involved in the biological process from hepatitis B to cirrhosis and HCC. N6-methyladenosine (m6A), as an epitranscriptomic modification of RNAs, can regulate the stability, splicing, degradation, transcription, and translation of downstream target RNAs in HBV and liver cancer cells. m6A regulators (writers, erasers, and readers) play an important role in the pathogenesis of HBV-associated HCC by regulating cell proliferation, apoptosis, migration, autophagy, differentiation, inflammation, angiogenesis, and tumor microenvironment. This review summarizes the current progress of m6A methylation in the molecular mechanisms, biological functions, and potential clinical implications of HBV-associated HCC.

Aim: The aim of our study was to investigate the potential predictive value of the combination of radiosensitivity gene signature and PD-L1 expression for the prognosis of locally advanced head and neck squamous cell carcinoma (HNSCC).Methods: The cohort was selected from The Cancer Genome Atlas (TCGA) and classified into the radiosensitive (RS) group and radioresistant (RR) group by a radiosensitivity-related gene signature. The cohort was also grouped as PD-L1-high or PD-L1-low based on PD-L1 mRNA expression. The least absolute shrinkage and selection operator (lasso)-based Cox model was used to select hub survival genes. An independent validation cohort was obtained from the Gene Expression Omnibus (GEO) database.Results: We selected 288 locally advanced HNSCC patients from TCGA. The Kaplan–Meier method found that the RR and PD-L1-high group had a worse survival than others (p = 0.033). The differentially expressed gene (DEG) analysis identified 553 upregulated genes and 486 downregulated genes (p < 0.05, fold change >2) between the RR and PD-L1-high group and others. The univariate Cox analysis of each DEG and subsequent lasso-based Cox model revealed five hub survival genes (POU4F1, IL34, HLF, CBS, and RNF165). A further hub survival gene-based risk score model was constructed, which was validated by an external cohort. We observed that a higher risk score predicted a worse prognosis (p = 0.0013). The area under the receiver operating characteristic curve (AUC) plots showed that this risk score model had good prediction value (1-year AUC = 0.684, 2-year AUC = 0.702, and 3-year AUC = 0.688). Five different deconvolution methods all showed that the B cells were lower in the RR and PD-L1-high group (p < 0.05). Finally, connectivity mapping analysis showed that the histone deacetylase (HDAC) inhibitor trichostatin A might have the potential to reverse the phenotype of RR and PD-L1-high in locally advanced HNSCC (p < 0.05, false discovery rate Conclusion: The combination of 31-gene signature and the PD-L1 mRNA expression had a potential predictive value for the prognosis of locally advanced HNSCC who had RT. The B cells were lower in the RR and PD-L1-high group. The identified risk gene signature of locally advanced HNSCC and the potential therapeutic drug trichostatin A for the RR and PD-L1-high group are worth being further studied in a prospective homogenous cohort.

Background: The association between long-term glycemic variability and diabetic retinopathy (DR) among patients with type 2 diabetes has not been clarified yet. Objective: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of DR in patients with type 2 diabetes. Design: A prospective cohort study of 315 patients (191 males and 124 females) with at least 3 measurements of HbA1c and GA prior to baseline was performed. Different GA and HbA1c variability markers were calculated, including coefficient of variation (CV), variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit HbA1c and GA variability and the risk of DR. Results: During a mean follow-up period of 3.42 years, 81 participants developed incident DR. Multivariate-adjusted hazard ratios (HRs) of DR across tertiles of GA-CV values were 1.00, 1.42, and 2.12 (P for trend=0.027), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of DR were found. Multivariable-adjusted HRs of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of DR after multivariate adjustment. Conclusion: The visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels. Disclosure J. Zhou: None. D. Dai: None. Y. Shen: None. J. Lu: None. Y. Wang: None. W. Zhu: None. Y. Bao: None. G. Hu: None. Funding National Key Research and Development Project of China (2018YFC2000802); Shanghai Municipal Education Commission (20161430); Shanghai Municipal Key Clinical Specialty

Objective. To investigate the effect of sevoflurane on the monophasic action potentials (MAPs) in isolated rat hearts after ischemia-reperfusion. Methods. Twenty-four healthy SD male rats, weighing 280–320 g, were randomly divided into three groups after successful preparation of a Langendorff isolated heart perfusion model with a stabilization period perfusion of 15 min with Krebs–Henseleit (K–H) fluid (n = 8): the control group (group A, continuously perfused with K–H fluid for 105 min), the ischemia-reperfusion group (group B, continuously perfused with K–H fluid for 15 min, and then exposed to 60 min of global ischemia induced by Thomas solution followed by 30 min of reperfusion), and the sevoflurane group (group C, K–H fluid contained 1.0 MAC sevoflurane, and other procedures were same as in group B). Heart rate (HR) and MAPs including time course (MAPD50 or MAPD90) of the epicardium (Epi) and endocardium (Endo) were recorded at the time of balance perfusion for 15 min (T0), continuous perfusion for 15 min (T1), reperfusion for 15 min/continuous perfusion for 105 min (T2), and reperfusion for 30 min/continuous perfusion for 120 min (T3), and the transmural dispersion of repolarization (TDR) was calculated. The incidence of arrhythmia, time for restoration of spontaneous heart beat, and duration of arrhythmia were recorded during the period of reperfusion. Results. HR in group B and group C was lower at T2 and T3 than that in group A, while that in group B was significantly lower than that in group A at T2 and T3, and HR in group C was higher than that in group B at T2 and T3 (P<0.05). There was no difference of TDR in each group at T0 and T1 (P>0.05), while TDR in group B was increased at T2 and T3 compared with that in group C and group A (P<0.05). TDR in group C was decreased compared with that in group B at T2 and T3 (P<0.05), while there was no such difference between group C and group A (P>0.05). The time for restoration of spontaneous heart beat and duration of arrhythmia in group C were shorter than those in group B (P<0.05), while cardiac arrhythmia scores in group B were higher than those in group C (P<0.05). There was no difference of MAPD50 in each group (P>0.05). The MAPD90 in group B was much longer than that in other groups at T2 and T3 (P<0.05), while there was no such difference between group C and group A (P>0.05). The prolonged MAPD90 at T2 and T3 in group B strikingly differed from that at T0 and T1 (P<0.05). Nevertheless, there was no such difference in other groups at different time points (P>0.05). Conclusion. Sevoflurane alleviates reperfusion arrhythmia induced by myocardial ischemia-reperfusion through the shortening of MPAD90 in isolated rat hearts.

The aim of the current study was to evaluate the influence of severe radiation-induced lymphopenia (RIL) on the outcomes of esophageal cancer (EC). A systematic review and meta-analysis was performed through the PRISMA guideline. Seventeen studies were included in the current systematic review, with eight included in the meta-analyses. Meta-analyses found that severe RIL was associated with lower pathologic complete response (pCR) rate (odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.30–0.66, I2 = 0%), inferior overall survival (OS) (hazard ratio (HR) = 1.50, 95% CI = 1.29–1.75, I2 = 6%), and worse progression-free survival (PFS) (HR = 1.70, 95% CI = 1.39–2.07, I2 = 0%) of EC patients. The lymphocyte nadir was found during 4–6 weeks after the start of radiotherapy. The leading dosimetric factors associated with severe RIL included larger PTV, higher dose to heart and body, and higher effective dose to the immune cells (EDIC). Clinical risk factors for RIL mainly comprised lower baseline ALC, higher tumor length and clinical stage, and distal EC. In conclusion, severe RIL might be associated with a lower pCR rate and worse OS and PFS of EC patients. Minimizing the dosimetric risk factors, especially in patients with clinical risk factors, might benefit their outcomes.

Background The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of lower extremity atherosclerotic disease (LEAD). Method We performed a prospective cohort study of 436 patients with type 2 diabetes (258 men and 178 women) with at least 3 measurements of HbA1c and GA prior to baseline investigation from the Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital. Different HbA1c and GA variability markers were calculated. Multivariable Cox proportional hazard regression models were used to demonstrate the association between visit-to-visit HbA1c and GA variability and the risk of incident or progressive LEAD. Results During a mean follow-up period of 3.77 years, 112 participants developed LEAD. Multivariate-adjusted hazard ratios (HRs) of LEAD across tertiles of GA-CV values were 1.00, 1.06 (95% confidence interval [CI] 0.65–1.75), and 1.71 (95% CI 1.07–2.73) (P for trend = 0.042), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of LEAD primary were found. Multivariate-adjusted HRs of LEAD for each 1 unit increase in GA-CV, GA-VIM and GA-ARV were 1.03 (95% CI 1.01–1.06), 1.32 (95% CI 1.03–1.69), and 1.07 (95%CI 1.01–1.15), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of LEAD. Conclusions Visit-to-visit variability of GA may be an optimal biomarker in relation to LEAD risk among patients with type 2 diabetes.

Supplemental Digital Content is available in the text, The aim of current study was to use Weighted Gene Coexpression Network Analysis (WGCNA) to identify hub genes related to the incidence and prognosis of KRAS mutant (MT) lung adenocarcinoma (LUAD). We involved 184 stage IIB to IV LUAD samples and 59 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. The R package “limma” was used to identify differentially expressed genes (DEGs). WGCNA and survival analyses were performed by R packages “WGCNA” and “survival,” respectively. The functional analyses were performed by R package “clusterProfiler” and GSEA software. Network construction and MCODE analysis were performed by Cytoscape_v3.6.1. Totally 2590 KRAS MT specific DEGs were found between LUAD and normal lung tissues, and 10 WGCNA modules were identified. Functional analysis of the key module showed the ribosome biogenesis related terms were enriched. We observed the expression of 8 genes were positively correlated to the worse survival of KRAS MT LUAD patients, the 7 of them were validated by Kaplan–Meier plotter database (kmplot.com/) (thymosin Beta 10 [TMSB10], ribosomal Protein S16 [RPS16], mitochondrial ribosomal protein L27 [MRPL27], cytochrome c oxidase subunit 6A1 [COX6A1], HCLS1-associated protein X-1 [HAX1], ribosomal protein L38 [RPL38], and ATP Synthase Membrane Subunit DAPIT [ATP5MD]). The GSEA analysis found mTOR and STK33 pathways were upregulated in KRAS MT LUAD (P

The aim of current study was to use competing risk model to assess whether medullary carcinoma of the breast (MCB) has a better prognosis than invasive ductal carcinomas of breast cancer (IDC), and to build a competing risk nomogram for predicting the risk of death of MCB. We involved 3,580 MCB patients and 319,566 IDC patients from Surveillance, Epidemiology, and End Results (SEER) database. IDC was found to have a worse BCSS than MCB (Hazard ratio (HR) > 1, p 1, p 0.05). After a penalized variable selection process, the SH model-based nomogram showed moderate accuracy of prediction by internal validation of discrimination and calibration with 1,000 bootstraps. In summary, MCB patients had a better prognosis than IDC patients. Interestingly, unmarried status in addition to expected risk factors such as larger tumor size and increasing number of positive lymph nodes were found to worsen the BCSS of MCB. We also established a competing risk nomogram as an easy-to-use tool for prognostic estimation of MCB patients.

Additional file 2: Supplemnetary Figures 1-6. Fig. S1. WNT/β-catenin signaling activates HSF1. Fig. S2. β-catenin has no effects on the RNA and protein half-life of HSF1. Fig. S3. The effect of microRNAs on HSF1 expression in CRC. Fig. S4. m6A modification of HSF1 mRNA. Fig. S5. The effects of miR455-3p and m6A modification on HSF1. Fig. S6. Volcano plot displays differentially regulated genes upon LiCl treatment.

Aim There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes. Methods This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2 years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR. Results After an average follow-up of 3.42 years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02–1.09), 1.69 (95% CI 1.24–2.32), and 1.13 (95%CI 1.04–1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR. Conclusions The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.

// 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.

Objective To investigate the effect of sevoflurane on the monophasic action potentials (MAPs) in isolated rat hearts after ischemia-reperfusion. Methods Twenty-four healthy SD male rats, weighing 280–320 g, were randomly divided into three groups after successful preparation of a Langendorff isolated heart perfusion model with a stabilization period perfusion of 15 min with Krebs–Henseleit (K–H) fluid (n = 8): the control group (group A, continuously perfused with K–H fluid for 105 min), the ischemia-reperfusion group (group B, continuously perfused with K–H fluid for 15 min, and then exposed to 60 min of global ischemia induced by Thomas solution followed by 30 min of reperfusion), and the sevoflurane group (group C, K–H fluid contained 1.0 MAC sevoflurane, and other procedures were same as in group B). Heart rate (HR) and MAPs including time course (MAPD50 or MAPD90) of the epicardium (Epi) and endocardium (Endo) were recorded at the time of balance perfusion for 15 min (T0), continuous perfusion for 15 min (T1), reperfusion for 15 min/continuous perfusion for 105 min (T2), and reperfusion for 30 min/continuous perfusion for 120 min (T3), and the transmural dispersion of repolarization (TDR) was calculated. The incidence of arrhythmia, time for restoration of spontaneous heart beat, and duration of arrhythmia were recorded during the period of reperfusion. Results HR in group B and group C was lower at T2 and T3 than that in group A, while that in group B was significantly lower than that in group A at T2 and T3, and HR in group C was higher than that in group B at T2 and T3 (P < 0.05). There was no difference of TDR in each group at T0 and T1 (P > 0.05), while TDR in group B was increased at T2 and T3 compared with that in group C and group A (P < 0.05). TDR in group C was decreased compared with that in group B at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The time for restoration of spontaneous heart beat and duration of arrhythmia in group C were shorter than those in group B (P < 0.05), while cardiac arrhythmia scores in group B were higher than those in group C (P < 0.05). There was no difference of MAPD50 in each group (P > 0.05). The MAPD90 in group B was much longer than that in other groups at T2 and T3 (P < 0.05), while there was no such difference between group C and group A (P > 0.05). The prolonged MAPD90 at T2 and T3 in group B strikingly differed from that at T0 and T1 (P < 0.05). Nevertheless, there was no such difference in other groups at different time points (P > 0.05). Conclusion Sevoflurane alleviates reperfusion arrhythmia induced by myocardial ischemia-reperfusion through the shortening of MPAD90 in isolated rat hearts.

Chemoresistance remains the uppermost disincentive for cancer treatment on account of many genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) are emerging players in promoting cancer initiation and progression. However, the regulation and function in chemoresistance are largely unknown. Herein, we identified ARHGAP5-AS1 as a lncRNA upregulated in chemoresistant gastric cancer cells and its knockdown reversed chemoresistance. Meanwhile, high ARHGAP5-AS1 expression was associated with poor prognosis of gastric cancer patients. Intriguingly, its abundance is affected by autophagy and SQSTM1 is responsible for transporting ARHGAP5-AS1 to autophagosomes. Inhibition of autophagy in chemoresistant cells, thus, resulted in the upregulation of ARHGAP5-AS1. In turn, it activated the transcription of ARHGAP5 in the nucleus by directly interacting with ARHGAP5 promoter. Interestingly, ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of ARHGAP5 mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. In summary, impaired autophagic degradation of lncRNA ARHGAP5-AS1 in chemoresistant cancer cells promoted chemoresistance. It can activate the transcription of ARHGAP5 in the nucleus and stimulate m6A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA in the cytoplasm by recruiting METTL3. Therefore, targeting ARHGAP5-AS1/ARHGAP5 axis might be a promising strategy to overcome chemoresistance in gastric cancer.

The aim of the present study was to use a competing risk model to analyze the prognostic value of mucinous adenocarcinoma (MAC) in patients with colorectal cancer (CRC). An additional aim was to construct nomograms for estimating the 3- and 5-year overall survival (OS) and cancer specific survival (CSS) rates of patients with primary CRC with MAC. The data were extracted from the Surveillance, Epidemiology, and End Results database, and a Multivariate Cox model and competing risk model were applied to assess the OS and CSS. Cox-based and competing risk-based nomograms were constructed and internally validated by discrimination and calibration, using the bootstrapping method with 1,000 times replicates. A total of 13,035 MAC and 61,958 non-mucinous adenocarcinoma (NMAC) CRC patients were enrolled in the present study. Compared with NMAC, MAC patients had a poorer OS and CSS time in the overall population, and in subgroups that comprised metastatic, non-metastatic, male, site of sigmoid colon, rectosigmoid junction and rectal CRC cases (HR>1; 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.

Glycated albumin (GA) and the variation of consecutive GA measurements are demonstrated to be associated with chronic diabetic complications. Compared to hemoglobin A1c, GA can provide more accurate glycemic information in patients with specific clinical conditions such as hemoglobin diseases, end-stage renal diseases on dialysis, or in patients who experience drastic changes in glucose level. Meanwhile, the use of GA is limited in several clinical situations such as obesity, autoimmune diseases, and predicting adverse pregnancy outcomes and arterial stiffness. This review summarized the clinical significance and research progress of GA and its variability.

Previous studies have suggested that increased opioid receptor κ1 (OPRK1) and opioid receptor δ1 (OPRD1) methylation levels are involved in Alzheimer's disease (AD). In the present study, the methylation levels of two opioid receptor genes, opioid receptor µ1 (OPRM1) and opioid related nociceptin receptor 1 (OPRL1), were analyzed for their association with AD. Gene methylation levels were measured using bisulfite pyrosequencing in DNA samples derived from blood samples of 51 AD patients and 63 controls. The results indicated that there were significantly elevated promoter methylation levels of OPRM1 and OPRL1 in AD (OPRM1: P=0.007; OPRL1: P=2.987x10‑6). Dual‑luciferase reporter gene assays demonstrated that the promoter fragments of these two genes were able to promote gene expression (OPRM1: Fold‑change=2.616, P=0.003; OPRL1: Fold change=11.395, P=0.007). In addition, receiver operating characteristic analyses further indicated that a methylation panel of four opioid receptor genes (area under the curve=0.848, sensitivity=0.723, and specificity=0.879) performed well in the prediction of AD. These results suggested that opioid receptor genes may be used as potential methylation biomarkers for the diagnosis of AD.

Androgen deprivation therapy (ADT) was an important management for metastatic prostate cancer. However, patients would finally progress to the metastatic castration-resistant prostate cancer (mCRPC) and lose sensitivity to ADT. In addition to lower testosterone level, ADT could cause anemia, which might impair the chemotherapy efficiency and worsen the outcomes of cancer patients. However, inconsistent results were found between anemia and mCRPC prognosis. Our study was the first systematic review to evaluate the influence of anemia in mCRPC prognosis. Thirteen studies with 6,484 samples were involved in this meta-analysis. We found anemia would worsen the Overall survival (OS) of mCRPC patients in both prognostic designed studies (HR = 1.55, 95% CI = 1.24-1.94) and retrospective designed studies (HR = 1.82, 95% CI = 1.52-2.18). Prognostic analyses also demonstrated that anemia associated with poor Progression free survival (PFS) (HR = 1.47, 95% CI = 1.22-1.75). In conclusion, we found that anemia was significantly associated with poor OS and PFS of mCRPC patients. Larger RCTs are needed for future study, especially for the evaluation of treatment value for anti-anemia in mCRPC.

Schizophrenia (SCZ) is one of the most complex mental illnesses affecting ~1% of the population worldwide. SCZ pathogenesis is considered to be a result of genetic as well as epigenetic alterations. Previous studies have aimed to identify the causative genes of SCZ. However, DNA methylation of long non-coding RNAs (lncRNAs) involved in SCZ has not been fully elucidated. In the present study, a comprehensive genome-wide analysis of DNA methylation was conducted using samples from two male patients with paranoid and undifferentiated SCZ, respectively. Methyl-CpG binding domain protein-enriched genome sequencing was used. In the two patients with paranoid and undifferentiated SCZ, 1,397 and 1,437 peaks were identified, respectively. Bioinformatic analysis demonstrated that peaks were enriched in protein-coding genes, which exhibited nervous system and brain functions. A number of these peaks in gene promoter regions may affect gene expression and, therefore, influence SCZ-associated pathways. Furthermore, 7 and 20 lncRNAs, respectively, in the Refseq database were hypermethylated. According to the lncRNA dataset in the NONCODE database, ~30% of intergenic peaks overlapped with novel lncRNA loci. The results of the present study demonstrated that aberrant hypermethylation of lncRNA genes may be an important epigenetic factor associated with SCZ. However, further studies using larger sample sizes are required.

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.

N6-methyladenosine (m6A) is the most abundant mRNA modification. With the development of antibody-based sequencing technologies and the findings of m6A-related “writers”, “erasers”, and “readers”, the relationships between m6A and mRNA metabolism are emerging. The m6A modification influences almost every step of RNA metabolism that comprises mRNA processing, mRNA exporting from nucleus to cytoplasm, mRNA translation, mRNA decay, and the biogenesis of long-non-coding RNA (lncRNA) and microRNA (miRNA). Recently, more and more studies have found m6A is associated with cancer, contributing to the self-renewal of cancer stem cell, promotion of cancer cell proliferation, and resistance to radiotherapy or chemotherapy. Inhibitors of m6A-related factors have been explored, and some of them were identified to inhibit cancer progression, indicating that m6A could be a target for cancer therapy. In this review, we are trying to summarize the regulation and function of m6A in human carcinogenesis.

// Mengjiao Han 1 , Dongjun Dai 1 , Neelum Aziz Yousafzai 1 , Faliang Wang 2 , Hanying Wang 1 , Qiying Zhou 1 , Haiqi Lu 1 , Wenxia Xu 2 , Lifeng Feng 2 , Hongchuan Jin 2 and Xian Wang 1 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China 2 Labortaory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China Correspondence to: Xian Wang, email: wangx118@zju.edu.cn Keywords: CXXC4, GDF15, apoptosis, gastric cancer Received: June 30, 2017 Accepted: September 05, 2017 Published: October 06, 2017 ABSTRACT Worldwide, gastric cancer is one of the most fatal cancers. Epigenetic alterations in gastric cancer play important roles in silencing of tumor suppressor genes. We previously found that CXXC finger protein 4 (CXXC4) was a novel tumor suppressor in gastric cancer. In this report, we demonstrated that CXXC4 inhibited growth of gastric cancer cells as a pro-apoptotic factor. This inhibition could be reversed by the pan-caspase inhibitor called Z-VAD-FMK. However, CXXC4 with mutations in its DNA binding domain failed to induce apoptosis. Growth differentiation factor 15 (GDF15) was identified as one of potential targets responsible for CXXC4-induced apoptosis. CXXC4 activated GDF15 transcription through enhancing the interaction of transcription factor Sp1 with GDF15 promoter. In summary, the nuclear protein CXXC4 activated apoptosis in gastric cancer through up-regulating its novel potential downstream target GDF15. GDF15 might be a promising target for clinical treatment of gastric cancer with CXXC4 deficiency.

Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 (LGALS2) is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the LGALS2 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of LGALS2 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that LGALS2 3279C>T played a protective role in CAD (P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82-0.97) and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71-0.94). The present case‑control study did not find a significant associa - tion between LGALS2 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that LGALS2 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.

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.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that affects ~2% of the population aged ≥65 years. The degeneration of dopamine neurons in the substantia nigra contributes to the pathogenesis of PD. Dopamine receptor D2 (DRD2) and dopamine receptor D3 (DRD3) are two key subtypes of dopamine receptors. The aim of our study was to evaluate the association between the polymorphisms of DRD2 and DRD3 genes and PD. Meta-analyses were conducted from 16 studies (46 stages) among 4,279 cases and 5,661 controls between PD and 9 polymorphisms (DRD2: rs1800497, rs1079597, rs6278, rs6279, rs273482, rs1799732 and rs1076563; DRD3: rs6280 and rs2134655). A significant association was observed between DRD3 rs2134655 polymorphism and PD [P=0.01, odds ratio (OR)=1.17, 95% confidence interval (CI): 1.03–1.32] and a borderline association was observed between DRD2 rs1800497 polymorphism and PD in Europeans (P=0.05, OR=1.13, 95% CI: 1.00–1.27). Findings of the current meta-analysis suggested that DRD3 rs2134655 polymorphism was associated with a 17% increased risk of PD and that DRD2 rs1800497 polymorphism had a potential to increase the risk of PD by 13% in Europeans. Future large-scale studies are required to confirm the ethnic difference of DRD2 rs1800497 polymorphism and to determine whether there were significant associations of PD with other polymorphisms in DRD2 and DRD3 genes.

Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of inflammatory syndromes. The aim of this study was to evaluate the association between IL1B polymorphisms and RA. A meta-analysis was performed on the association between three IL1B polymorphisms (IL1B-31: rs1143627; IL1B-511: rs16944; IL1B + 3954: rs1143634) and RA. A trend of significant association was observed between IL1B + 3954 and RA (p = 0.06, odd ratio (OR) = 1.19, 95% confidential interval (CI) = 1.00-1.42). A significant association was found in Europeans under the dominant model between IL1B-511T and RA (p = 0.03, OR = 0.89, 95% CI = 0.81-0.99). Our meta-analysis indicated that IL1B ? 511-T played a protective role against RA in Europeans, and that IL1B + 3954-T had the potential to increase the risk of RA. Future large-scale studies should be considered to confirm the association between IL1B polymorphisms and RA.

Parkinson disease (PD) is a neurological disorder with huge destruction to human body, which affects approximately 2% of the population aged 65 years or older. As antioxidants in the stress defence systems, glutathione S-transferases (GSTs) are dimeric cytosolic enzymes with an important role in the pathogenesis of PD. The aim of this study was to evaluate the association between the polymorphisms of GST genes and PD. Meta-analyses were conducted from 17 studies (38 stages) among 3419 cases and 5686 controls between four polymorphisms (GSTT1 deletion polymorphism; GSTM1 deletion polymorphism; GSTP1-104: rs1695; GSTP1-114: rs1799811) and PD. There is no significant association between the four GST gene variants and PD. A further subgroup study by ethnicity observed a risky role of GSTM1 deletion polymorphism with PD in Europeans (p = 0.013, OR = 1.126, 95% CI = 1.025-1.236), and a protective role of GSTM1 deletion polymorphism with PD in Latin Americans (p = 0.032, OR = 0.750, 95% CI = 0.577-0.975). Our meta-analysis suggested that GSTM1 deletion polymorphism increased the risk of PD in Europeans, but reduced the risk of PD in Latin Americans. Future large-scale studies might be needed to confirm the ethnic difference of GSTM1 deletion polymorphism, and to check whether there was significant association of PD for other GST genetic polymorphisms.

AIM The aim of this study was to assess whether rs1333049 was associated with coronary heart disease (CHD) in Han Chinese. METHODS This case-control study was involved with 599 CHD patients and 591 non-CHD controls. Meanwhile, a comprehensive meta-analysis was also conducted to establish the contribution of rs1333049 to CHD. RESULTS Our results showed that rs1333049 increased the risk of CHD by 38% (OR=1.38, 95% CI=1.18-1.62). A breakdown analysis by gender further indicated that rs1333049 increased the risk of CHD in men by 29% (OR=1.29, 95% CI=1.05-1.58) and in women by 64% (OR=1.64, 95% CI=1.25-2.16). A follow-up subgroup analysis by age showed there was a significant association between rs1333049 and CHD in women younger than 65 (≤55 years: p=0.001, 55-65 years: p=0.008) and in men aged between 55 and 65 years (p=0.005). Our meta-analysis was involved with 21 studies (25 stages) among 20969 cases and 34114 controls. Our results showed that rs1333049 led to a significantly increased risk of CHD (OR=1.30, 95% CI=1.21-1.39). Further subgroup analyses by ethnicity showed rs1333049 increased the CHD risk by 30% in Europeans (OR=1.30, 95% CI=1.16-1.47) and 27% in Asians (OR=1.27, 95% CI=1.22-1.33). CONCLUSIONS Our case-control study and meta-analysis suggest that rs1333049 is a useful risk marker of CHD.

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.

Low density lipoprotein receptor (LDLR) can regulate cholesterol metabolism by removing the excess low density lipoprotein cholesterol (LDL-C) in blood. Since cholesterol metabolism is often disrupted in coronary heart disease (CHD),LDLRas a candidate gene of CHD has been intensively studied. The goal of our study is to evaluate the overall contribution ofLDLRrs2228671 polymorphism to the risk of CHD by combining the genotyping data from multiple case-control studies. Our meta-analysis is involved with 8 case-control studies among 7588 cases and 9711 controls to test the association betweenLDLRrs2228671 polymorphism and CHD. In addition, we performed a case-control study ofLDLRrs2228671 polymorphism with the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T allele was significantly associated with a reduced risk of CHD (P=0.0005, odds ratio (OR) = 0.83, and 95% confidence interval (95% CI) = 0.75–0.92). However, rs2228671-T allele frequency was rare (1%) and was not associated with CHD in Han Chinese (P=0.49), suggesting an ethnic difference ofLDLRrs2228671 polymorphism. Meta-analysis has established rs2228671 as a protective factor of CHD in Europeans. The lack of association in Chinese reflects an ethnic difference of this genetic variant between Chinese and European populations.

Background Recent studies have shown Growth differentiation factor–15 (GDF-15) that is a member of the transforming growth factor β (TGF-β) superfamily might be a potential predictive cytokine for the prognosis of Acute coronary syndrome (ACS). However, there are discrepancies in these studies. Methods Publication searches of the PubMed/Medline and EMBASE databases were performed without any time or ethnicity restrictions. The inclusion and exclusion criteria, when clear, were addressed. Random effects models were used for all analyses. Publication bias was tested using funnel plots and the Egger test. Results We identified eight eligible studies that provided mortality data. Five of these studies provided recurrent myocardial infarction (MI) data. The maximal duration of follow-up ranged from 6 months to 6 years. A significant association was found between the patients with the highest and lowest GDF-15 levels (overall analyses) in terms of mortality (p

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.

Objectives Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of this case–control study was to explore whether the CpG-SNPs of the thrombotic pathway genes contributed to the risk of CHD. Methods and materials A total of 784 CHD patients and 738 healthy controls were recruited in the current association study, which evaluated 7 CpG-SNPs of the thrombotic pathway genes. The CpG-SNPs included THBS4 rs17878919, CYP2C19 rs12773342, P2RY12 rs1491974, ITGA2 rs26680, FGB rs2227389, F7 rs510317 and F5 rs2269648. SNP genotyping was performed with a Sequenom Mass Spectrometry Genetic Analyzer. Results Our results demonstrated that CYP2C19 rs12773342 polymorphism was significantly associated with CHD in the recessive model ( χ 2 = 5.41, df = 1, P = 0.020, OR = 1.455, 95% CI = 1.060–1.996). A breakdown analysis by age showed that the association of CYP2C19 rs12773342 with CHD was mainly found in individuals aged 55–65 (genotype: χ 2 = 7.93, df = 2, P = 0.019; allele: χ 2 = 4.45, df = 1, P = 0.035). In addition, we also observed a significant association between F7 rs510317 polymorphism and CHD in males (genotype: χ 2 = 7.24, df = 2, P = 0.027). There was no significant association with CHD for the remaining CpG-SNPs. Conclusion Our results supported that the CYP2C19 rs12773342 and F7 rs510317 polymorphisms were associated with CHD in the Han Chinese population.

As a member of the opioid family, κ-opioid receptors play important role in cognitive and learning functions. The purpose of this study was to evaluate the association of OPRK1 promoter methylation with Alzheimer's disease (AD). OPRK1 DNA methylation levels of 48 cases and 58 well matched controls were measured using the bisulphite pyrosequencing technology. Our results showed that there was a significant correlation between three CpG sites on the OPRK1 promoter region (r>=0.715, p

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

Schizophrenia (SCZ) is a complex mental disorder contributed by both genetic and epigenetic factors. Long noncoding RNAs (lncRNAs) was recently found playing an important regulatory role in mental disorders. However, little was known about the DNA methylation of lncRNAs, although numerous SCZ studies have been performed on genetic polymorphisms or epigenetic marks in protein coding genes. We presented a comprehensive genome wide DNA methylation study of both protein coding genes and lncRNAs in female patients with paranoid and undifferentiated SCZ. Using the methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), 8,163 and 764 peaks were identified in paranoid and undifferentiated SCZ, respectively (p

Background Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA. Methods Meta-analyses were performed between RA and 3 TAP2 coding polymorphisms that comprised TAP2-379Ile > Val (rs1800454), TAP2-565Ala > Thr (rs2228396) and TAP2-665Thr > Ala (rs241447). The meta-analyses were involved with 9 studies (24 individual studies) among 973 cases and 965 controls. Results Meta-analyses showed that TAP2-379Ile allele was significantly associated with an increased risk of RA (p = 0.0002, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.18-1.74). This association was further shown only in the dominant model (p = 0.006, OR = 1.59, 95% CI = 1.14-2.22). Subgroup analyses by ethnicity revealed that the association of TAP2-379Ile was significant in Asians (p = 0.03, OR = 1.38, 95% CI = 1.04-1.83). In addition, another significant association of TAP2-565Thr allele with RA was observed in Europeans (p = 0.002, OR = 1.62, 95% CI = 1.20-2.20). Conclusions Our meta-analyses suggested that TAP2-379Ile allele was significantly associated with a 59% increased risk in the dominant effect model. Subgroup analyses by ethnicity showed that TAP2-379-Ile increased the risk of RA by 38% in Asians and TAP2-565Thr increased the risk of RA by 38% in Europeans. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2097080313124700

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.

Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 (LGALS2) is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the LGALS2 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of LGALS2 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that LGALS2 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82–0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71–0.94). The present case-control study did not find a significant association between LGALS2 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that LGALS2 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.

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.

Background Mild cognitive impairment (MCI) is the intermediate stage of the cognitive changes between normal aging and dementia. KLOTH is an age-related gene that may contribute to the risk of MCI. The aim of our study was to explore the association between KLOTHO promoter methylation and MCI in Xinjiang Uygur and Han populations. Methods DNA methylation assay was performed using the bisulphite pyrosequencing technology among 96 Uygur (48 MCI and 48 controls) and 96 Han (48 MCI and 48 controls) Chinese individuals from Xinjiang province of China. Results We found significant association between KLOTHO promoter methylation and MCI in the Han Chinese (CpG1: p = 3.77E-06; CpG2: p = 1.91E-07; CpG3: p = 5.83E-07; CpG4: p = 2.23E-05; CpG5: p = 3.03E-06) but not in the Uygur Chinese. Higher KLOTHO promoter methylation levels were found in Han MCI patients than Uygur MCI patients for all the five CpGs (adjusted p values by age < 0.02). Conclusion Our results showed that KLOTHO promoter hypermethylation contributed to the MCI risk in Xinjiang Han Chinese but not in Xinjiang Uygur Chinese. The population difference of KLOTHO methylation in the risk of MCI required further investigation in the future.