Effect of the CYBA C242T Polymorphism on Preeclampsia Pathogenesis in the Chinese Population.

BACKGROUND: Although the mechanisms responsible for the pathogenesis of preeclampsia (PE) have not been entirely clarified, oxidative stress is thought to be its leading cause. As a major component responsible for reactive oxygen species (ROS) production during oxidative stress, p22phox, encoded by CYBA, is an essential subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The aim of this study was to investigate whether CYBA expression and its polymorphism are associated with PE. METHODS: Expression of CYBA was analysed in placentas from PE and control groups, as well as in HTR-8/SVneo cells stimulated with CoCl2 and TNF-α. Then, the CYBA C242T polymorphism in 1184 patients with PE and 1421 healthy controls was genotyped using the TaqMan probe, and the different distributions identified were confirmed by a case‒control association study. RESULTS: Expression of CYBA mRNA and protein in the placenta of pregnant women with PE was significantly increased compared to controls. Expression of CYBA mRNA was also increased in HTR-8/SVneo cells collected after 24 h of separate stimulation with cobalt chloride and TNF-α. There was no significant difference in the distribution of the C242T locus genotype and CYBA allele frequency between the case group and control group (P > 0.05). CONCLUSIONS: CYBA may play a role in the pathogenesis of oxidative stress in PE, in which it may function by cooperating with the TNF-α-related inflammatory pathway. Although no discrepant distribution of the CYBA C242T polymorphism in the Chinese population was detected, it is necessary to examine multiple CYBA SNPs in diverse populations and perform functional experiments to gain further insights into its pathogenesis.

Polymorphisms of TGF-ß1 and TGF-ß3 in Chinese women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-ß (TGF-ß) superfamily play key roles in the homeostasis of pancreatic ß-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-ß1, TGF-ß3 and the risk to GDM in Chinese women. METHODS: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-ß1 (rs4803455) and TGF-ß3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. RESULTS: An increased frequency of TGF-ß3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-ß1 rs4803455 and TGF-ß3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). CONCLUSIONS: The AA and AG genotype of TGF-ß3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

The Value of lncRNA HULC as a Prognostic Factor for Survival of Cancer Outcome: A Meta-Analysis.

AIMS: Growing evidence from recent studies has shown that lncRNA HULC plays a role in the development of multiple carcinomas. This meta-analysis aimed to analyze available data to identify the prognostic value of HULC in multiple tumors. METHODS: A systematic search was performed by using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) computerized databases from inception to Nov 30, 2016. The quality of the publications was assessed according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE and PRISMA. Pooled hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to summarize the effect. RESULTS: A total of ten studies with 1077 cancer patients were pooled in the present meta-analysis to evaluate the prognostic value of HULC in multiple tumors. High expression levels of HULC were demonstrated to be associated with poor overall survival (OS) (HR=2.44, 95%CI: 1.96-3.03, P=0.000). Subgroup analysis showed that cancer type (digestive or non-digestive disease), residence region (China), sample size (more or less than 100) and follow-up months (more or less than 60) did not alter the predictive value of HULC on OS in various cancers. Additionally, increased HULC expression was found to be moderately associated with tumor stage and progression (III/IV vs. I/II: HR=1.59, 95% CI: 1.31-1.92, P<0.00001). Furthermore, elevated HULC expression significantly predicted distant metastasis (HR=3.90, 95% CI: 1.89-8.02, P=0.0002) and lymph node metastasis (HR=2.04, 95% CI: 1.03-4.05, P=0.04) respectively. No significant heterogeneity was observed among studies except lymph node metastasis. CONCLUSION: The results indicate that HULC expression level is an independent prognostic biomarker for unfavorable OS and metastasis in general tumors.

The role of VCAM-1 in diabetic retinopathy: A systematic review and meta-analysis.

OBJECTIVE: Vascular cell adhesion molecule-1 (VCAM-1) plays a regulatory role in inflammatory diseases. However, the exact role of VCAM-1 in diabetic retinopathy (DR) remains unclear, and there is a lack of meta-analyses. METHODS: The role of VCAM-1 in DR was screened by database searching. A random effects model was used, and the estimated mean difference was evaluated. RESULTS: Twenty articles were included. The level of VCAM-1 increased significantly in the DR group compared with the control group (SMD: 0.67, 95 % CI: 0.34-1.01, P < 0.0001). VCAM-1 levels correlated with sample size and DR type, method and severity based on subgroup analysis. CONCLUSION: A high level of VCAM-1 is present in DR patients and is related to the severity of DR. Therefore, VCAM-1 is a potential detection biomarker for DR.

mirTools: microRNA profiling and discovery based on high-throughput sequencing.

miRNAs are small, non-coding RNA that negatively regulate gene expression at post-transcriptional level, which play crucial roles in various physiological and pathological processes, such as development and tumorigenesis. Although deep sequencing technologies have been applied to investigate various small RNA transcriptomes, their computational methods are far away from maturation as compared to microarray-based approaches. In this study, a comprehensive web server mirTools was developed to allow researchers to comprehensively characterize small RNA transcriptome. With the aid of mirTools, users can: (i) filter low-quality reads and 3/5' adapters from raw sequenced data; (ii) align large-scale short reads to the reference genome and explore their length distribution; (iii) classify small RNA candidates into known categories, such as known miRNAs, non-coding RNA, genomic repeats and coding sequences; (iv) provide detailed annotation information for known miRNAs, such as miRNA/miRNA*, absolute/relative reads count and the most abundant tag; (v) predict novel miRNAs that have not been characterized before; and (vi) identify differentially expressed miRNAs between samples based on two different counting strategies: total read tag counts and the most abundant tag counts. We believe that the integration of multiple computational approaches in mirTools will greatly facilitate current microRNA researches in multiple ways. mirTools can be accessed at http://centre.bioinformatics.zj.cn/mirtools/ and http://59.79.168.90/mirtools.

MagicViewer: integrated solution for next-generation sequencing data visualization and genetic variation detection and annotation.

New sequencing technologies, such as Roche 454, ABI SOLiD and Illumina, have been increasingly developed at an astounding pace with the advantages of high throughput, reduced time and cost. To satisfy the impending need for deciphering the large-scale data generated from next-generation sequencing, an integrated software MagicViewer is developed to easily visualize short read mapping, identify and annotate genetic variation based on the reference genome. MagicViewer provides a user-friendly environment in which large-scale short reads can be displayed in a zoomable interface under user-defined color scheme through an operating system-independent manner. Meanwhile, it also holds a versatile computational pipeline for genetic variation detection, filtration, annotation and visualization, providing details of search option, functional classification, subset selection, sequence association and primer design. In conclusion, MagicViewer is a sophisticated assembly visualization and genetic variation annotation tool for next-generation sequencing data, which can be widely used in a variety of sequencing-based researches, including genome re-sequencing and transcriptome studies. MagicViewer is freely available at http://bioinformatics.zj.cn/magicviewer/.

Impact of SLC23A1 and SLC23A2 Polymorphisms on the Risk for Preeclampsia in a Chinese Han Population.

Solute carrier family 23 member 1 (SVCT1) and solute carrier family 23 member 2 (SVCT2), encoded by SLC23A1 and SLC23A2, may be associated with preeclampsia (PE). The purpose of this study was to investigate the association between polymorphisms of SLC23A1 and SLC23A2 and PE in Chinese Han population. The primers and double-labeled probes were designed according to the SNPs of rs10063949 in SLC23A1, rs6133175 and rs1279683 in SLC23A2. Genomic DNA was extracted from peripheral blood of 2,066 subjects (1,029 with PE and 1,037 without PE), and Taqman real-time PCR was used to detect the three SNPs. We observed a significant difference in genotypic frequency of the SLC23A2 rs6133175 polymorphism (χ2=8.08, p=0.02) between PE patients and controls, while no significant differences were found in the allelic frequencies (χ2=1.45, p=0.23). Then we fractionized these samples into the dominant model of the allele G (GG/AG+AA group) or the recessive model of the A allele (AA/AG+GG group), and observed a significant difference under the recessive model of the A allele (p=0.01, OR=0.71, 95% CI 0.55-0.92). Furthermore, there were no significant differences in the genotypic and allelic frequencies of rs10063949 and rs1279683 between PE patients and controls (for rs10063949, χ2=2.96, p=0.23 by genotype, χ2=2.11, p=0.15 by allele; for rs1279683, χ2=1.52, p=0.47 by genotype, χ2=0.64, p=0.44 by allele). We first found that SLC23A2 rs6133175 may be the certain genetic polymorphisms modulating their effects in the development of PE in a Chinese Han population and the AG or GG genotypes may be a risk factor for PE.

A review of key cytokines based on gene polymorphism in the pathogenesis of pre-eclampsia.

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal-fetal interface, and genetic and environmental factors, the etiopathology of pre-eclampsia (PE) remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in PE, and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE.

PGA4genomics for comparative genome assembly based on genetic algorithm optimization.

New sequencing technologies greatly facilitate the large-scale bacterial genome sequencing by reducing cost. However, a considerable bottleneck is in the finishing phase, where dozens to hundreds of gaps need to be closed. In this study, we constructed a web server (PGA4genomics) to help users automate gap closing based on comparative genomic syntenies. Extensive evaluations showed that it significantly outperforms previous methods and can produce highly accurate layout result, especially when assembling genomes that are only moderately related. The availability of such a platform would greatly benefit the research community working on bacterial genomics. PGA4genomics can be accessed at two mirror sites http://centre.bioinformatics.zj.cn:8080/pga or http://59.79.168.90:8080/pga.

Value of ABCG2 Q141K and Q126X genotyping in predicting risk of preeclampsia in Chinese Han women population.

Hyperuricemia (HUA) in women with preeclampsia (PE) not only indicates a reminder of severity but also contributes directly to the pathogenesis of PE. ATP-binding cassette subfamily G member 2 (ABCG2) has a very strong effect on the serum urate concentrations. Our aim was to investigate the association between polymorphisms of ABCG2 with PE in Chinese Han female population. A cohort of 793 preeclamptic women (466 PE with HUA and 327 PE without HUA) and 744 normal pregnant women recruited in this study were genotyped for genetic distribution of Q141K (rs2231142) and Q126X (72552713) in ABCG2 by the TaqMan allelic discrimination real-time PCR. There was no statistically significant difference of genotypic and allelic frequencies between PE and the normal pregnant women in Q141K (Χ2 = 1.11, P = 0.58 by genotype; Χ2 = 0.32, P = 0.57 by allele) and Q126X (P = 0.33 by genotype; P = 0.33 by allele), and no significant difference was found in the genetic distribution of Q141K and Q126X between PE with HUA, PE without HUA and controls. Additionally, this study observed no significant difference in genotypic and allelic distribution between early/late-onset PE with/without HUA or mild/severe PE with/without HUA and control subgroups. Based on our findings, the ABCG2 Q141K and Q126X polymorphisms may not be associated with PE in Chinese Han women.

Effects of Klotho polymorphisms on Preeclampsia risk in a case-control study.

Preeclampsia (PE) is a serious disorder of human pregnancy and always is accompanied with multi-organ disorder, which severely threatens the health of both the mothers and the offspring. The oxidative stress and genetic factors involves in the development of PE. The Klotho encodes Klotho protein that is capable of increasing resistance to oxidative stress. Thus, we designed this case-control study to investigate the association between Klotho polymorphisms and the susceptibility to PE in Chinese Han women. Two single nucleotide polymorphisms (SNPs) (rs1207568 and rs564481) in Klotho were selected to be genotyped in 1002 PE patients and 1384 normal controls with TaqMan allelic discrimination real-time PCR technology. There were no significant differences in genotypic or allelic frequencies at both polymorphic sites between PE patients and controls (rs1207568: χ2 = 2.386, p = 0.303 by genotype, χ2 = 2.357, p = 0.125, OR = 1.127, 95%CI 0.968-1.312 by allele; rs564481: χ2 = 1.195, p = 0.550 by genotype, χ2 = 0.018, p = 0.894, OR = 1.010, 95%CI 0.875-1.165 by allele). Furthermore, we divided the cases into mild vs severe and early-onset vs late-onset subgroups and then analyzed the relationships between these subgroups and the control group respectively. As a consequence, no significant differences were found for both SNPs in each case. These results suggested that the genetic variants of rs1207568 and rs564481 in Klotho may not play a pivotal role in the pathogenesis of PE in Chinese Han women.