Differential gene expression patterns between smokers and non-smokers: cause or consequence?
Ontology highlight
ABSTRACT:
SUBMITTER: Vink JM
PROVIDER: S-EPMC5347870 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Differential gene expression patterns between smokers and non-smokers: cause or consequence?
Vink Jacqueline M JM Jansen Rick R Brooks Andy A Willemsen Gonneke G van Grootheest Gerard G de Geus Eco E Smit Jan H JH Penninx Brenda W BW Boomsma Dorret I DI
Addiction biology 20151122 2
The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex-smokers were available from two population-based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hu ...[more]
Similar Datasets
Project description:Identifying similarities between patterns of differential gene expression provides an opportunity to identify similarities between the experimental and biological conditions that give rise to these gene expression alterations. The growing volume of gene expression data in open data repositories such as the NCBI Gene Expression Omnibus (GEO) presents an opportunity to identify these gene expression similarities on a large scale across a diverse collection of datasets. We have developed a fast, pattern-based computational approach, named openSESAME (Search of Expression Signatures Across Many Experiments), that identifies datasets enriched in samples that display coordinate differential expression of a query signature. Importantly, openSESAME performs this search without prior knowledge of the phenotypic or experimental groups in the datasets being searched. This allows openSESAME to identify perturbations of gene expression that are due to phenotypic attributes that may not have been described in the sample annotation included in the repository. : To demonstrate the utility of openSESAME, we used gene expression signatures of two biological perturbations to query a set of 75,164 human expression profiles that were generated using Affymetrix microarrays and deposited in GEO. The first query, using a signature of estradiol treatment, identified experiments in which estrogen signaling was perturbed and also identified differences in estrogen signaling between estrogen receptor-positive and -negative breast cancers. The second query, which used a signature of silencing of the transcription factor p63 (a key regulator of epidermal differentiation), identified datasets related to stratified squamous epithelia or epidermal diseases such as melanoma.openSESAME is a tool for leveraging the growing body of publicly available microarray data to discover relationships between different biological states based on common patterns of differential gene expression. These relationships may serve to generate hypotheses about the causes and consequences of specific patterns of observed differential gene expression.
| S-EPMC3203354 | biostudies-literature
Project description:Hygienic behavior is a complex, genetically-based quantitative trait that serves as a key defense mechanism against parasites and diseases in Apis mellifera. Yet, the genomic basis and functional pathways involved in the initiation of this behavior are still unclear. Deciphering the genomic basis of hygienic behavior is a prerequisite to developing an extensive repertoire of genetic markers associated to the performance level of this quantitative trait. To fill this knowledge gap, we performed an RNA-seq on brain samples of 25 honeybees per hives from five hygienic and three non-hygienic hives.This analysis revealed that a limited number of functional genes are involved in honeybee hygienic behavior. The genes identified, and especially their location in the honeybee genome, are consistent with previous findings. Indeed, the genomic sequences of most differentially expressed genes were found on the majority of the QTL regions associated to the hygienic behavior described in previous studies. According to the Gene Ontology annotation, 15 genes are linked to the GO-terms DNA or nucleotide binding, indicating a possible role of these genes in transcription regulation. Furthermore, GO-category enrichment analysis revealed that electron carrier activity is over-represented, involving only genes belonging to the cytochrome P450. Cytochrome P450 enzymes' overexpression can be explained by a disturbance in the regulation of expression induced by changes in transcription regulation or sensitivity to xenobiotics. Over-expressed cytochrome P450 enzymes could potentially degrade the odorant pheromones or chemicals that normally signal the presence of a diseased brood before activation of the removal process thereby inhibit hygienic behavior.These findings improve our understanding on the genetics basis of the hygienic behavior. Our results show that hygienic behavior relies on a limited set of genes linked to different regulation patterns (expression level and biological processes) associated with an over-expression of cytochrome P450 genes.
| S-EPMC4491870 | biostudies-literature
Project description:Cigarette smoking is the leading risk factor for lung cancer, which accounts for the highest number of cancer-related mortalities worldwide in men and women. Individuals with a history of smoking are 15-30 times more likely to develop lung cancer compared with those who do not smoke. However, our understanding of the underlying molecular mechanisms that contribute to lung tumorigenesis in smokers versus non-smokers remains incomplete. In order to investigate such mechanisms, the present study aimed to systemically interrogate microarray datasets from tumor biopsies and matching normal tissues from stage I and II lung adenocarcinoma patients who had never smoked or were current smokers. The gene expression analysis identified 422 (99 upregulated and 323 downregulated) and 534 (174 upregulated and 360 downregulated) differentially-expressed genes from the never-smokers and current smokers, respectively, and the two groups shared 277 genes that exhibited similar trends of alteration. These genes encode regulators that are involved in a variety of cellular functions, including collagen metabolism and homeostasis of caveolae plasma membranes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes characterization indicated that biological pathways, including extracellular matrix-receptor interaction and cell migration and proliferation, were all affected in the lung cancer patients regardless of the smoking status. However, smoking induced a unique gene expression pattern characterized by upregulation of cell cycle regulators (CDK1, CCNB1 and CDC20), as well as significantly affected biological networks, including p53 signaling pathways. Taken together, these findings suggest novel mechanistic insights, and provide an improved understanding of the smoking-induced molecular alterations that contribute to the pathogenesis of lung adenocarcinoma.
| S-EPMC4533670 | biostudies-literature
Project description:Tonotopic differences in the structure and physiological function, e.g., synapse number, membrane properties, Ca2+ channels, Ca2+ dependence of exocytosis and vesicle pool replenishment of inner hair cells (IHCs) along the longitudinal cochlear axis have recently been discovered, suggesting different gene expression patterns of IHCs. To determine whether IHCs present different gene expression patterns along the longitudinal cochlear axis, apical and basal IHCs were collected separately using the suction pipette technique from adult mouse cochleae for RNA-seq and genome-wide transcriptome analysis. We found 689 annotated genes showed more than 2-fold increase in expression. Interestingly, 93.4% of the differentially expressed genes (DEGs) was upregulated in apical IHCs. Although a subset of genes that related to IHC machinery and deafness were found to be differentially expressed, a gradient of gene expression was indeed detected in Ocm, Pvalb, Prkd1, Fbxo32, Nme2, and Sncg, which may play putative roles in the Ca2+ buffering and survival regulation. The expression of these genes was validated by real-time quantitative PCR (RT-qPCR) or immunostaining. We conclude that IHCs from different mouse cochlear longitudinal position have different gene expression profiles. Our data might serve as a valuable resource for exploring the molecular mechanisms underlying different biological properties as well as the survival regulation of IHCs.
| S-EPMC6985465 | biostudies-literature
Project description:Smoking is the second leading cause of preventable death in the United States. Cohort epidemiological studies have demonstrated that women are more vulnerable to cigarette-smoking induced diseases than their male counterparts, however, the molecular basis of these differences has remained unknown. In this study, we explored if there were differences in the gene expression patterns between male and female smokers, and how these patterns might reflect different sex-specific responses to the stress of smoking. Using whole genome microarray gene expression profiling, we found that a substantial number of oxidant related genes were expressed in both male and female smokers, however, smoking-responsive genes did indeed differ greatly between male and female smokers. Gene set enrichment analysis (GSEA) against reference oncogenic signature gene sets identified a large number of oncogenic pathway gene-sets that were significantly altered in female smokers compared to male smokers. In addition, functional annotation with Ingenuity Pathway Analysis (IPA) identified smoking-correlated genes associated with biological functions in male and female smokers that are directly relevant to well-known smoking related pathologies. However, these relevant biological functions were strikingly overrepresented in female smokers compared to male smokers. IPA network analysis with the functional categories of immune and inflammatory response gene products suggested potential interactions between smoking response and female hormones. Our results demonstrate a striking dichotomy between male and female gene expression responses to smoking. This is the first genome-wide expression study to compare the sex-specific impacts of smoking at a molecular level and suggests a novel potential connection between sex hormone signaling and smoking-induced diseases in female smokers.
| S-EPMC4303254 | biostudies-literature
Project description:BACKGROUND: Cigarette smoking is well-known to associate with accelerated skin aging as well as cardiovascular disease and lung cancer, in large part due to oxidative stress. Because metabolites are downstream of genetic variation, as well as transcriptional changes and post-translational modifications of proteins, they are the most proximal reporters of disease states or reversal of disease states. METHODS: In this study, we explore the potential effects of commonly available oral supplements (containing antioxidants, vitamins and omega-3 fatty acids) on the metabolomes of smokers (n = 11) compared to non-smokers (n = 17). At baseline and after 12 weeks of supplementation, metabolomic analysis was performed on serum by liquid and gas chromatography with mass spectroscopy (LC-MS and GC-MS). Furthermore, clinical parameters of skin aging, including cutometry as assessed by three dermatologist raters blinded to subjects' age and smoking status, were measured. RESULTS: Long-chain fatty acids, including palmitate and oleate, decreased in smokers by 0.76-fold (P = 0.0045) and 0.72-fold (P = 0.0112), respectively. These changes were not observed in non-smokers. Furthermore, age and smoking status showed increased glow (P = 0.004) and a decrease in fine wrinkling (P = 0.038). Cutometry showed an increase in skin elasticity in smokers (P = 0.049) but not in non-smokers. Complexion analysis software (VISIA) revealed decreases in the number of ultraviolet spots (P = 0.031), and cutometry showed increased elasticity (P = 0.05) in smokers but not non-smokers. CONCLUSIONS: Additional future work may shed light on the specific mechanisms by which long-chain fatty acids can lead to increased glow, improved elasticity measures and decreased fine wrinkling in smokers' skin. Our study provides a novel, medicine-focused application of available metabolomic technology to identify changes in sera of human subjects with oxidative stress, and suggests that oral supplementation (in particular, commonly available antioxidants, vitamins and omega-3 fatty acids) affects these individuals in a way that is unique (compared to non-smokers) on a broad level.
| S-EPMC3392760 | biostudies-literature
Project description:The issue of potential confounding factors is critical to the development of any approach to radiation biodosimetry, and has not been fully addressed for gene expression-based approaches.As a step in this direction, we have investigated the effect of smoking on the global radiation gene expression response in ex vivo-irradiated peripheral blood cells using microarray analysis. We also evaluated the ability of gene expression signatures to predict the radiation exposure level of ex vivo-exposed samples from smokers and non-smokers of both genders.We identified eight genes with a radiation response that was significantly affected by smoking status, and confirmed an effect of smoking on the radiation response of the four and a half LIM domains 2 (FHL2) gene using quantitative real-time polymerase chain reaction. The performance of our previously defined 74-gene signature in predicting the radiation dose to samples in this study was unaffected by differences in gender or smoking status, however, giving 98% correct prediction of dose category. This is the same accuracy as that found in the original study from which the signature was derived, using different donors.The results support the development of peripheral blood gene expression as a viable strategy for radiation biodosimetry.
| S-EPMC3580190 | biostudies-literature
Project description:Interventions: Group 1: Quantitative Expression Analysis of the proteom and gene Expression of Primary Tumor, normal tissue, and metastases
Primary outcome(s): Disease associated Proteins and Genes
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: basic science
| 2431957 | ecrin-mdr-crc
Project description:Mitochondrial DNA copy number is strictly regulated during development as naive cells differentiate into mature cells to ensure that specific cell types have sufficient copies of mitochondrial DNA to perform their specialised functions. Mitochondrial DNA haplotypes are defined as specific regions of mitochondrial DNA that cluster with other mitochondrial sequences to show the phylogenetic origins of maternal lineages. Mitochondrial DNA haplotypes are associated with a range of phenotypes and disease. To understand how mitochondrial DNA haplotypes induce these characteristics, we used four embryonic stem cell lines that have the same set of chromosomes but possess different mitochondrial DNA haplotypes. We show that mitochondrial DNA haplotypes influence changes in chromosomal gene expression and affinity for nuclear-encoded mitochondrial DNA replication factors to modulate mitochondrial DNA copy number, two events that act synchronously during differentiation. Global DNA methylation analysis showed that each haplotype induces distinct DNA methylation patterns, which, when modulated by DNA demethylation agents, resulted in skewed gene expression patterns that highlight the effectiveness of the new DNA methylation patterns established by each haplotype. The haplotypes differentially regulate ?-ketoglutarate, a metabolite from the TCA cycle that modulates the TET family of proteins, which catalyse the transition from 5-methylcytosine, indicative of DNA methylation, to 5-hydroxymethylcytosine, indicative of DNA demethylation. Our outcomes show that mitochondrial DNA haplotypes differentially modulate chromosomal gene expression patterns of naive and differentiating cells by establishing mitochondrial DNA haplotype-specific DNA methylation patterns.
| S-EPMC5592988 | biostudies-literature
Project description:PURPOSE: Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. We report the first study of global and ECM-focused gene transcription differentials between GFAP-negative lamina cribrosa (LC) cells from normal and POAG human donors. METHODS: GFAP-negative LC cell lines were generated from the optic nerve tissue of four normal (n=4) and four POAG (n=4) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was performed using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. RESULTS: 183 genes were upregulated by greater than 1.5 fold and 220 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, transforming growth factor beta 1 (TGFbeta1), secreted acid protein cysteine rich (SPARC), periostin (POSTN), thrombospondin-1 (THBS1), cartilage linking protein-1 (CRTL-1), and collagen type I (COL1A1), collagen type V (COL5A1), and collagen type XI (COL11A1). Downregulated ECM genes in POAG included fibulin 1 (FBLN1), decorin (DCN), and collagen type XVIII (COL18A1). All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. CONCLUSIONS: This study reports for the first time that POAG LC cells in-vitro demonstrate upregulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling in POAG and an attractive target for molecular therapeutic strategies in the future.
| S-EPMC2622717 | biostudies-literature