Expression Analysis and Genotyping of DGKZ: a GWAS-derived Risk Gene for Schizophrenia

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2019 May 16

PMID 31087244

Citations 4

Authors

Somayeh Alinaghi

Elham Alehabib

Amir Hossein Johari

Fatemeh Vafaei

Shima Salehi

Hossein Darvish

Hamid Ghaedi

Affiliations

Soon will be listed here.

Abstract

Schizophrenia (SCZ) is a disabling and severe mental illness characterized by abnormal social behavior and disrupted emotions. Similar to other neuropsychological disorders, both genetics and environmental factors interplay so as to develop SCZ. It is acknowledged that genes such as DGKZ are involved in lipid signaling pathways that are the basis of neural activities, memory, and learning and are considered as candidate loci for SCZ. The aim of the present study was to evaluate the expression level and genotypes of DGKZ in patients with SCZ and controls. We used q-PCR to measure the relative expression of DGKZ in blood. To determine DGKZ-rs7951870 genotypes, tetra-ARMS PCR was used. Our results showed a significant difference in DGKZ mRNA ratio between SCZ patients and healthy controls (P = 2 × 10). Also, we showed that rs7951870-TT genotype was strongly associated with increased DGKZ expression level (P = 0.038). In conclusion, our findings revealed dysregulation of DGKZ in SCZ patients and a significant correction between the gene expression and DGKZ variant rs7951870.

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References

Topham M, Prescott S . Mammalian diacylglycerol kinases, a family of lipid kinases with signaling functions. J Biol Chem. 1999; 274(17):11447-50. DOI: 10.1074/jbc.274.17.11447. View

Ye S, Dhillon S, Ke X, Collins A, Day I . An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res. 2001; 29(17):E88-8. PMC: 55900. DOI: 10.1093/nar/29.17.e88. View

Zhang J, Moseley A, Jegga A, Gupta A, Witte D, Sartor M . Neural system-enriched gene expression: relationship to biological pathways and neurological diseases. Physiol Genomics. 2004; 18(2):167-83. DOI: 10.1152/physiolgenomics.00220.2003. View

Weidenhofer J, Bowden N, Scott R, Tooney P . Altered gene expression in the amygdala in schizophrenia: up-regulation of genes located in the cytomatrix active zone. Mol Cell Neurosci. 2005; 31(2):243-50. DOI: 10.1016/j.mcn.2005.09.013. View

Schmidt-Kastner R, van Os J, Steinbusch H, Schmitz C . Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res. 2006; 84(2-3):253-71. DOI: 10.1016/j.schres.2006.02.022. View

Messias E, Chen C, Eaton W . Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin North Am. 2007; 30(3):323-38. PMC: 2727721. DOI: 10.1016/j.psc.2007.04.007. View

Raben D, Tu-Sekine B . Nuclear diacylglycerol kinases: regulation and roles. Front Biosci. 2007; 13:590-7. DOI: 10.2741/2704. View

Kim S, Choi K, Baykiz A, Gershenfeld H . Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex. BMC Genomics. 2007; 8:413. PMC: 2211497. DOI: 10.1186/1471-2164-8-413. View

Lencz T, Lambert C, DeRosse P, Burdick K, Morgan T, Kane J . Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia. Proc Natl Acad Sci U S A. 2007; 104(50):19942-7. PMC: 2148402. DOI: 10.1073/pnas.0710021104. View

10.

Potkin S, Turner J, Guffanti G, Lakatos A, Fallon J, Nguyen D . A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophr Bull. 2008; 35(1):96-108. PMC: 2643953. DOI: 10.1093/schbul/sbn155. View

11.

Gejman P, Sanders A, Duan J . The role of genetics in the etiology of schizophrenia. Psychiatr Clin North Am. 2010; 33(1):35-66. PMC: 2826121. DOI: 10.1016/j.psc.2009.12.003. View

12.

Ikeda M, Aleksic B, Kinoshita Y, Okochi T, Kawashima K, Kushima I . Genome-wide association study of schizophrenia in a Japanese population. Biol Psychiatry. 2010; 69(5):472-8. DOI: 10.1016/j.biopsych.2010.07.010. View

13.

Kim Y, Zerwas S, Trace S, Sullivan P . Schizophrenia genetics: where next?. Schizophr Bull. 2011; 37(3):456-63. PMC: 3080692. DOI: 10.1093/schbul/sbr031. View

14.

Rietschel M, Mattheisen M, Degenhardt F, Muhleisen T, Kirsch P, Esslinger C . Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe. Mol Psychiatry. 2011; 17(9):906-17. DOI: 10.1038/mp.2011.80. View

15.

Bergen S, Petryshen T . Genome-wide association studies of schizophrenia: does bigger lead to better results?. Curr Opin Psychiatry. 2012; 25(2):76-82. PMC: 3771358. DOI: 10.1097/YCO.0b013e32835035dd. View

16.

Sinclair D, Fullerton J, Webster M, Weickert C . Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants. PLoS One. 2012; 7(3):e31720. PMC: 3302776. DOI: 10.1371/journal.pone.0031720. View

17.

Pedersen C, McGrath J, Mortensen P, Petersen L . The importance of father's age to schizophrenia risk. Mol Psychiatry. 2013; 19(5):530-1. DOI: 10.1038/mp.2013.69. View

18.

Cheng C, Loh E, Lin C, Chan C, Lan T . Birth seasonality in schizophrenia: effects of gender and income status. Psychiatry Clin Neurosci. 2013; 67(6):426-33. DOI: 10.1111/pcn.12076. View

19.

Hosak L . New findings in the genetics of schizophrenia. World J Psychiatry. 2013; 3(3):57-61. PMC: 3832862. DOI: 10.5498/wjp.v3.i3.57. View

20.

Hall M, Levy D, Salisbury D, Haddad S, Gallagher P, Lohan M . Neurophysiologic effect of GWAS derived schizophrenia and bipolar risk variants. Am J Med Genet B Neuropsychiatr Genet. 2013; 165B(1):9-18. PMC: 3984007. DOI: 10.1002/ajmg.b.32212. View