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Metabolic Brain Disease

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19.03.2020 | Original Article

Phosphoinositide-3-kinase regulatory subunit 1 gene polymorphisms are associated with schizophrenia and bipolar disorder in the Han Chinese population

verfasst von: Jiao Huang, Zhaoxia Chen, Lulu Zhu, Xulong Wu, Xiaojing Guo, Jialei Yang, Jianxiong Long, Li Su

Erschienen in: Metabolic Brain Disease | Ausgabe 5/2020

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Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric disorders that share many genetic risk factors. This study aimed to investigate the association of phosphoinositide-3-kinase regulatory subunit1 (PIK3R1) gene rs3756668 and rs3730089 polymorphisms with SCZ and BD risks and determine the expression levels of PIK3R1. A total of 548 SCZ cases, 512 BD cases, and 598 healthy controls were included in this study. Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform, and quantitative reverse transcription polymerase chain reaction was conducted to examine the mRNA expression of PIK3R1. The genotypic distribution of rs3756668 in the BD group was significantly different from that in the healthy controls (P = 0.038). After adjustment for gender and age was made, rs3730089 was significantly associated with the risk of SCZ [AA/(AG + GG): OR = 2.25, P_adj = 0.040; AA/GG: OR = 2.27, P_adj = 0.038]. The SNP rs3756668 was associated with the susceptibility of BD (AA+GG/AG: OR = 0.73, P = 0.011) and the association remained after adjusting for gender and age. The mRNA level of PIK3R1 was significantly upregulated in patients with BD compared with that in the control group (P < 0.001). In terms of the diagnostic value of PIK3R1 for BD, the receiver operating characteristic curve analysis showed an area under the curve of 0.809 with 74.0% sensitivity and 73.9% specificity. PIK3R1 may be the shared susceptibility gene of SCZ and BD and may be a potential diagnostic biomarker for BD.

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Alexandrov PN, Zhao Y, Jaber V, Cong L, Lukiw WJ (2017) Deficits in the proline-rich synapse-associated Shank3 protein in multiple neuropsychiatric disorders. Front Neurol 8:670. https://doi.org/10.3389/fneur.2017.00670 CrossRefPubMedPubMedCentral

Almind K, Delahaye L, Hansen T, Van Obberghen E, Pedersen O, Kahn CR (2002) Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85alpha. Proc Natl Acad Sci U S A 99:2124–2128. https://doi.org/10.1073/pnas.042688799 CrossRefPubMedPubMedCentral

Beaulieu JM, Gainetdinov RR, Caron MG (2007) The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci 28:166–172. https://doi.org/10.1016/j.tips.2007.02.006 CrossRefPubMed

Bowden NA, Scott RJ, Tooney PA (2008) Altered gene expression in the superior temporal gyrus in schizophrenia. BMC Genomics 9:199. https://doi.org/10.1186/1471-2164-9-199 CrossRefPubMedPubMedCentral

Bresee LC, Majumdar SR, Patten SB, Johnson JA (2010) Prevalence of cardiovascular risk factors and disease in people with schizophrenia: a population-based study. Schizophr Res 117:75–82. https://doi.org/10.1016/j.schres.2009.12.016 CrossRefPubMed

Burghardt KJ, Seyoum B, Dass SE, Sanders E, Mallisho A, Yi Z (2018) Association of protein Kinase B (AKT) DNA hypermethylation with maintenance atypical antipsychotic treatment in patients with bipolar disorder. Pharmacotherapy 38:428–435. https://doi.org/10.1002/phar.2097 CrossRefPubMedPubMedCentral

Castano-Betancourt MC et al (2016) Novel genetic variants for cartilage thickness and hip osteoarthritis. PLoS Genet 12:e1006260. https://doi.org/10.1371/journal.pgen.1006260 CrossRefPubMedPubMedCentral

Chen YG (2018) Research progress in the pathogenesis of Alzheimer's disease. Chin Med J 131:1618–1624. https://doi.org/10.4103/0366-6999.235112 CrossRefPubMedPubMedCentral

Chen M et al (2010) Genetic variations of the PI3K-AKT-mTOR pathway and clinical outcome in muscle invasive and metastatic bladder cancer patients. Carcinogenesis 31:1387–1391. https://doi.org/10.1093/carcin/bgq110 CrossRefPubMedPubMedCentral

Chen C et al (2014) Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. Bipolar Disord 16:790–799. https://doi.org/10.1111/bdi.12255 CrossRefPubMedPubMedCentral

Cross-Disorder Group of the Psychiatric Genomics C et al (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 45:984–994. https://doi.org/10.1038/ng.2711 CrossRef

Dwivedi Y et al (2008) Lower phosphoinositide 3-kinase (PI 3-kinase) activity and differential expression levels of selective catalytic and regulatory PI 3-kinase subunit isoforms in prefrontal cortex and hippocampus of suicide subjects. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 33:2324–2340. https://doi.org/10.1038/sj.npp.1301641 CrossRef

Elkaim E et al (2016) Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: a cohort study. J Allergy Clin Immunol 138:210–218 e219. https://doi.org/10.1016/j.jaci.2016.03.022 CrossRefPubMed

Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA (2004) Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36:131–137. https://doi.org/10.1038/ng1296 CrossRefPubMed

Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606–619. https://doi.org/10.1038/nrg1879 CrossRefPubMed

Fatjo-Vilas M et al (2016) Involvement of NRN1 gene in schizophrenia-spectrum and bipolar disorders and its impact on age at onset and cognitive functioning. World J Biol Psychiat: the official journal of the World Federation of Societies of Biological Psychiatry 17:129–139. https://doi.org/10.3109/15622975.2015.1093658 CrossRef

Goes FS, Rongione M, Chen YC, Karchin R, Elhaik E, Bipolar Genome S, Potash JB (2011) Exonic DNA sequencing of ERBB4 in bipolar disorder. PLoS One 6:e20242. https://doi.org/10.1371/journal.pone.0020242 CrossRefPubMedPubMedCentral

Guo X et al (2018) Influence of CTNNB1 rs2953 polymorphism on schizophrenia susceptibility in Chinese Han population through modifying miR-485 binding to CTNNB1. Genes Brain Behav:e12524. https://doi.org/10.1111/gbb.12524

Jauhar S et al (2017) A test of the Transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia. JAMA Psychiat 74:1206–1213. https://doi.org/10.1001/jamapsychiatry.2017.2943 CrossRef

Karadogan AH, Arikoglu H, Gokturk F, Iscioglu F, Ipekci SH (2018) PIK3R1 gene polymorphisms are associated with type 2 diabetes and related features in the Turkish population. Adv Clin Exp Med: official organ Wroclaw Medical University. https://doi.org/10.17219/acem/68985

Khan RA et al (2016) Analysis of association between common variants in the SLCO6A1 gene with schizophrenia, bipolar disorder and major depressive disorder in the Han Chinese population. World J Biol Psychiat: the official journal of the World Federation of Societies of Biological Psychiatry 17:140–146. https://doi.org/10.3109/15622975.2015.1126676 CrossRef

Kolomeets NS, Orlovskaya DD, Rachmanova VI, Uranova NA (2005) Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia: a postmortem morphometric study. Synapse 57:47–55. https://doi.org/10.1002/syn.20153 CrossRefPubMed

Krivosheya D et al (2008) ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms. J Biol Chem 283:32944–32956. https://doi.org/10.1074/jbc.M800073200 CrossRefPubMedPubMedCentral

Li L, Plummer SJ, Thompson CL, Tucker TC, Casey G (2008) Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk. Clin Cancer Res: an official journal of the American Association for Cancer Research 14:633–637. https://doi.org/10.1158/1078-0432.CCR-07-1211 CrossRef

Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373:234–239. https://doi.org/10.1016/S0140-6736(09)60072-6 CrossRefPubMed

Liu Y, Li Z, Zhang M, Deng Y, Yi Z, Shi T (2013) Exploring the pathogenetic association between schizophrenia and type 2 diabetes mellitus diseases based on pathway analysis. BMC Med Genet 6(Suppl 1):S17. https://doi.org/10.1186/1755-8794-6-S1-S17 CrossRef

Liu J, He J, Cheng M, Cao H, Zhang X (2019) Prevalence, sociodemographic, and clinical correlates of older chinese patients with deficit schizophrenia. J Geriatr Psychiatry Neurol 32:298–303. https://doi.org/10.1177/0891988719870321 CrossRefPubMed

Long J et al (2014) The prevalence of schizophrenia in mainland China: evidence from epidemiological surveys. Acta Psychiatr Scand 130:244–256. https://doi.org/10.1111/acps.12296 CrossRefPubMed

Malodobra M, Pilecka A, Gworys B, Adamiec R (2011) Single nucleotide polymorphisms within functional regions of genes implicated in insulin action and association with the insulin resistant phenotype. Mol Cell Biochem 349:187–193. https://doi.org/10.1007/s11010-010-0673-5 CrossRefPubMed

Martín-Peña A, Acebes A, Rodríguez J-R, Sorribes A, de Polavieja GG, Fernández-Fúnez P, Ferrús A (2006) Age-independent synaptogenesis by phosphoinositide 3 kinase. J Neurosci 26:10199–10208. https://doi.org/10.1523/JNEUROSCI.1223-06.2006 CrossRefPubMedPubMedCentral

Merikangas KR et al (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68:241–251. https://doi.org/10.1001/archgenpsychiatry.2011.12 CrossRefPubMedPubMedCentral

Munkholm K, Peijs L, Vinberg M, Kessing LV (2015) A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder. Transl Psychiatry 5:e614. https://doi.org/10.1038/tp.2015.110 CrossRefPubMedPubMedCentral

Nie L, Zhaom Z, Wen X, Luo W, Ju T, Ren A, Wu B, London ED, Li J (2018) Factors affecting the occurrence of psychotic symptoms in chronic methamphetamine users. J Addict Dis 37:202–210. https://doi.org/10.1080/10550887.2019.1661752 CrossRefPubMed

Psychiatric GCBDWG (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 43:977–983. https://doi.org/10.1038/ng.943 CrossRef

Ramanan VK et al (2014) APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study. Mol Psychiatry 19:351–357. https://doi.org/10.1038/mp.2013.19 CrossRefPubMed

Schizophrenia Psychiatric Genome-Wide Association Study C (2011) Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43:969–976. https://doi.org/10.1038/ng.940 CrossRef

Shi S, Leites C, He D, Schwartz D, Moy W, Shi J, Duan J (2014) MicroRNA-9 and microRNA-326 regulate human dopamine D2 receptor expression, and the microRNA-mediated expression regulation is altered by a genetic variant. J Biol Chem 289:13434–13444. https://doi.org/10.1074/jbc.M113.535203 CrossRefPubMedPubMedCentral

Smilowitz S, Aftab A, Aebi M, Levin J, Tatsuoka C, Sajatovic M (2019) Age-related differences in medication adherence, symptoms, and stigma in poorly adherent adults with bipolar disorder. J Geriatr Psychiatry Neurol:891988719874116–891988719874116. https://doi.org/10.1177/0891988719874116

Sodersten K, Palsson E, Ishima T, Funa K, Landen M, Hashimoto K, Agren H (2014) Abnormality in serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in mood-stabilized patients with bipolar disorder: a study of two independent cohorts. J Affect Disord 160:1–9. https://doi.org/10.1016/j.jad.2014.01.009 CrossRefPubMed

Strejilevich S, Szmulewicz A, Igoa A, Marengo E, Caravotta P, Martino D (2019) Episodic density, subsyndromic symptoms, and mood instability in late-life bipolar disorders: a 5-year follow-up study. Int J Geriatr Psychiatry 34:950–956. https://doi.org/10.1002/gps.5094 CrossRefPubMed

Teixeira AL, Colpo GD, Fries GR, Bauer IE, Selvaraj S (2018) Biomarkers for bipolar disorder: current status and challenges ahead. Expert Rev Neurother:1–15. https://doi.org/10.1080/14737175.2019.1550361

Tohda C, Nakanishi R, Kadowaki M (2006) Learning deficits and agenesis of synapses and myelinated axons in phosphoinositide-3 kinase-deficient mice. Neuro-Signals 15:293–306. https://doi.org/10.1159/000108936 CrossRefPubMed

Wang LE et al (2012) Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to endometrial cancer and clinical outcomes. J Cancer Res Clin Oncol 138:377–385. https://doi.org/10.1007/s00432-011-1103-0 CrossRefPubMed

Wen Z et al (2016a) Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population. Am J Med Genet B Neuropsychiatr Genet: the official publication of the International Society of Psychiatric Genetics 171B:468–478. https://doi.org/10.1002/ajmg.b.32428 CrossRef

Wen Z et al (2016b) Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population. J Affect Disord 194:180–187. https://doi.org/10.1016/j.jad.2016.01.034 CrossRefPubMed

Winnay JN, Kahn CR (2011) PI 3-kinase regulatory subunits as regulators of the unfolded protein response. Methods Enzymol 490:147–158. https://doi.org/10.1016/B978-0-12-385114-7.00009-X CrossRefPubMedPubMedCentral

Yamada T et al (2017) Resting-state functional connectivity-based biomarkers and functional MRI-based Neurofeedback for psychiatric disorders: a challenge for developing theranostic biomarkers. Int J Neuropsychopharmacol 20:769–781. https://doi.org/10.1093/ijnp/pyx059 CrossRefPubMedPubMedCentral

Zhu S et al (2017) Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder. Proc Natl Acad Sci U S A 114:10479–10484. https://doi.org/10.1073/pnas.1700689114 CrossRefPubMedPubMedCentral

Titel: Phosphoinositide-3-kinase regulatory subunit 1 gene polymorphisms are associated with schizophrenia and bipolar disorder in the Han Chinese population
verfasst von: Jiao Huang
Zhaoxia Chen
Lulu Zhu
Xulong Wu
Xiaojing Guo
Jialei Yang
Jianxiong Long
Li Su
Publikationsdatum: 19.03.2020
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 5/2020
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-020-00552-z

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Phosphoinositide-3-kinase regulatory subunit 1 gene polymorphisms are associated with schizophrenia and bipolar disorder in the Han Chinese population

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