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https://www.readbyqxmd.com/read/28094813/a-methylome-wide-mqtl-analysis-reveals-associations-of-methylation-sites-with-gad1-and-hdac3-snps-and-a-general-psychiatric-risk-score
#1
D M Ciuculete, A E Boström, S Voisin, H Philipps, O E Titova, M Bandstein, L Nikontovic, M J Williams, J Mwinyi, H B Schiöth
Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28045928/altered-epithelial-gene-expression-in-peripheral-airways-of-severe-asthma
#2
Akul Singhania, Hitasha Rupani, Nivenka Jayasekera, Simon Lumb, Paul Hales, Neil Gozzard, Donna E Davies, Christopher H Woelk, Peter H Howarth
Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2...
2017: PloS One
https://www.readbyqxmd.com/read/28030643/targeted-sequencing-of-fkbp5-in-suicide-attempters-with-bipolar-disorder
#3
Marie E Breen, Sophia C Gaynor, Eric T Monson, Kelly de Klerk, Meredith G Parsons, Terry A Braun, Adam P DeLuca, Peter P Zandi, James B Potash, Virginia L Willour
FKBP5 is a critical component of the Hypothalamic-Pituitary-Adrenal (HPA) axis, a system which regulates our response to stress. It forms part of a complex of chaperones, which inhibits binding of cortisol and glucocorticoid receptor translocation to the nucleus. Variations in both the HPA axis and FKBP5 have been associated with suicidal behavior. We developed a systematic, targeted sequencing approach to investigate coding and regulatory regions in or near FKBP5 in 476 bipolar disorder suicide attempters and 473 bipolar disorder non-attempters...
2016: PloS One
https://www.readbyqxmd.com/read/28025095/a-cross-species-study-of-heterogeneity-in-fear-extinction-learning-in-relation-to-fkbp5-variation-and-expression-implications-for-the-acute-treatment-of-posttraumatic-stress-disorder
#4
Isaac R Galatzer-Levy, Raül Andero, Takehito Sawamura, Tanja Jovanovic, Santiago Papini, Kerry J Ressler, Seth Davin Norrholm
Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM)...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28018293/dynamic-changes-in-dna-methylation-occur-during-the-first-year-of-life-in-preterm-infants
#5
Chinthika Piyasena, Jessy Cartier, Nadine Provençal, Tobias Wiechmann, Batbayar Khulan, Raju Sunderasan, Gopi Menon, Jonathan R Seckl, Rebecca M Reynolds, Elisabeth B Binder, Amanda J Drake
BACKGROUND: Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28007534/fkbp5-polymorphism-is-associated-with-insulin-resistance-in-children-and-adolescents-with-obesity
#6
Marta Fichna, Izabela Krzyśko-Pieczka, Magdalena Żurawek, Bogda Skowrońska, Danuta Januszkiewicz-Lewandowska, Piotr Fichna
OBJECTIVE: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis...
December 19, 2016: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28002634/fkbp5-polymorphisms-influence-pre-learning-stress-induced-alterations-of-learning-and-memory
#7
Phillip R Zoladz, Alison M Dailey, Hannah E Nagle, Miranda K Fiely, Brianne E Mosley, Callie M Brown, Tessa J Duffy, Amanda R Scharf, McKenna B Earley, Boyd R Rorabaugh
FK506 binding protein 51(FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder, and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role...
December 21, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27968728/evidence-mounting-for-gene-by-environment-interactions-at-the-fkbp5-locus-predicting-psychiatric-symptoms
#8
Thorhildur Halldorsdottir
No abstract text is available yet for this article.
December 1, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27941579/early-life-stress-fkbp5-polymorphisms-and-quantitative-glycemic-traits
#9
Anna Suarez, Jari Lahti, Eero Kajantie, Johan G Eriksson, Katri Räikkönen
OBJECTIVE: Early life stress (ELS) has been shown to influence health later in life. Functioning of the hypothalamic-pituitary-adrenal (HPA) axis, regulated partly by FKBP5 gene, may moderate these effects. We examined whether FKBP5 single nucleotide polymorphisms (SNPs) interact with ELS on type 2 diabetes, cardiovascular disease, and quantitative glycemic traits. METHODS: 1,728 Helsinki Birth Cohort Study participants born 1934-44 were genotyped for FKBP5 SNPs (rs1360780, rs9394309, rs9470080), administered a 2-h (75 g) oral glucose tolerance test and a questionnaire on physician-diagnosed and medication use for chronic diseases at a mean age of 61...
December 9, 2016: Psychosomatic Medicine
https://www.readbyqxmd.com/read/27923569/gender-differences-of-b-cell-signature-related-to-estrogen-induced-ifi44l-baff-in-systemic-lupus-erythematosus
#10
Hongye Fan, Guangfeng Zhao, Deshan Ren, Fei Liu, Guanjun Dong, Yayi Hou
Systemic lupus erythematosus (SLE) possesses a gender-dependent incidence characterized by a male/female ratio 1:9. B-cell, a vital part of the immune system, plays an important role in pathogenesis of SLE. Thus, we hypothesize that gender differences of B cells may exist in SLE and relate to the onset and the progression of SLE. Here, we showed that the genes expression pattern is similar between healthy female and male. However, SLE female and SLE male showed more upregulated genes, in which the trendline of SLE male is higher than that of SLE female...
December 5, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27915167/examining-fkbp5-mrna-expression-in-human-ipsc-derived-neural-cells
#11
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation...
January 2017: Psychiatry Research
https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#12
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27760575/the-interactive-effects-of-child-maltreatment-and-the-fk506-binding-protein-5-gene-fkbp5-on-dissociative-symptoms-in-adolescence
#13
Fatima Tuba Yaylaci, Dante Cicchetti, Fred A Rogosch, Okan Bulut, Susan R Hetzel
The FK506 binding protein 5 gene (FKBP5) has been associated with susceptibility to pathogenic effects of childhood trauma including dissociative symptoms. This study examines the impact of maltreatment on dissociative tendencies in adolescence as moderated by the FKBP5 gene. Dissociative symptoms and variation within FKBP5 were assessed in a high-risk, low socioeconomic status community sample of 279 maltreated and 171 nonmaltreated adolescents. Following the assignment of haplotypes across four single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080), individuals with one or more copies of the CATT haplotype (N = 230) were grouped together and compared to individuals with zero copies of this haplotype (N = 185)...
October 20, 2016: Development and Psychopathology
https://www.readbyqxmd.com/read/27754486/association-of-fkbp5-polymorphisms-and-resting-state-activity-in-a-frontotemporal-parietal-network
#14
R A Bryant, K L Felmingham, B Liddell, P Das, G S Malhi
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles...
October 18, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27752945/pharmacogenetics-and-imaging-pharmacogenetics-of-antidepressant-response-towards-translational-strategies
#15
REVIEW
Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
December 2016: CNS Drugs
https://www.readbyqxmd.com/read/27709495/evidence-for-a-link-between-fkbp5-fkbp5-early-life-social-relations-and-alcohol-drinking-in-young-adult-rats-and-humans
#16
Ingrid Nylander, Aniruddha Todkar, Linnea Granholm, Maria Vrettou, Megha Bendre, Wout Boon, Henrik Andershed, Catherine Tuvblad, Kent W Nilsson, Erika Comasco
Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27691985/childhood-adversity-and-epigenetic-regulation-of-glucocorticoid-signaling-genes-associations-in-children-and-adults
#17
Audrey R Tyrka, Kathryn K Ridout, Stephanie H Parade
Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects...
October 3, 2016: Development and Psychopathology
https://www.readbyqxmd.com/read/27690835/microrna-320a-predicts-chronic-axial-and-widespread-pain-development-following-motor-vehicle-collision-in-a-stress-dependent-manner
#18
Sarah D Linnstaedt, Kyle D Riker, Margaret G Walker, Jennifer E Nyland, Erin Zimny, Christopher Lewandowski, Phyllis L Hendry, Kathia Damiron, Claire Pearson, Marc-Anthony Velilla, Jeffrey Jones, Robert A Swor, Robert Domeier, Samuel A McLean
Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC)...
October 2016: Journal of Orthopaedic and Sports Physical Therapy
https://www.readbyqxmd.com/read/27688096/the-mir-367-3p-increases-sorafenib-chemotherapy-efficacy-to-suppress-hepatocellular-carcinoma-metastasis-through-altering-the-androgen-receptor-signals
#19
Junjie Xu, Hui Lin, Gonghui Li, Yin Sun, Jiang Chen, Liang Shi, Xiujun Cai, Chawnshang Chang
The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3'UTR of MDM2 to decrease MDM2 protein expression...
October 2016: EBioMedicine
https://www.readbyqxmd.com/read/27680313/novel-roles-of-fkbp5-in-muscle-alteration-induced-by-gravity-change-in-mice
#20
Takeshi Shimoide, Naoyuki Kawao, Yukinori Tamura, Hironobu Morita, Hiroshi Kaji
Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions...
October 21, 2016: Biochemical and Biophysical Research Communications
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