title: The impact of HLA-G 3' UTR variants and sHLA-G on risk and clinical correlates of schizophrenia.
abstract: The Major Histocompatibility Complex (MHC)/Human Leukocyte Antigen (HLA) is known to influence the pathogenesis of several complex human diseases resulting from gene-environmental interactions. Recently, it has emerged as one of the risk determinants of schizophrenia. The HLA-G protein (a non-classical MHC class I molecule), encoded by the HLA-G gene, is shown to play important role in embryonic development. Importantly, its genetic variations and aberrant expression have been implicated in pregnancy complications like preeclampsia, inflammation, and autoimmunity. Converging evidence implicates these phenomena as risk mechanisms of schizophrenia. However, the functional implications of HLA-G in schizophrenia are yet to be empirically examined. The impact of two functional polymorphisms [14bp Insertion/Deletion (INDEL) and +3187 A>G] and soluble HLA-G (sHLA-G) levels on schizophrenia risk was evaluated. In this exploratory study, the Ins/Ins genotype of 14bp INDEL was found to confer a strong risk for schizophrenia. Further, low levels of sHLA-G were shown to have a significant impact on Clinical Global Impression (CGI) severity in people with schizophrenia.
authors: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Ashwini
authors: A
authors: Rajasekaran
authors: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Venkataram
authors: V
authors: Shivakumar
authors: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Sunil V
authors: SV
authors: Kalmady
authors: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Janardhanan C
authors: JC
authors: Narayanaswamy
authors: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Manjula
authors: M
authors: Subbana
authors: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Deepthi
authors: D
authors: Venugopal
authors: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Anekal C
authors: AC
authors: Amaresha
authors: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors: Ganesan
authors: G
authors: Venkatasubramanian
authors: Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Victoria, Australia; Department of Psychiatry, The Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia.
authors: Michael
authors: M
authors: Berk
authors: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. Electronic address: monozeet@gmail.com.
authors: Monojit
authors: M
authors: Debnath
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: Development; HLA-G; Hallucinations; Infection; Inflammation; Schizophrenia