The impact of HLA-G 3́ UTR variants and sHLA-G on risk and clinical correlates of schizophrenia

• Published in: Human immunology Vol. 77; no. 12; pp. 1166 - 1171
• Main Authors: Rajasekaran, Ashwini, Shivakumar, Venkataram, Kalmady, Sunil V, Narayanaswamy, Janardhanan C, Subbana, Manjula, Venugopal, Deepthi, Amaresha, Anekal C, Venkatasubramanian, Ganesan, Berk, Michael, Debnath, Monojit
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: 3' Untranslated Regions - genetics; Adolescent; Adult; Allergy and Immunology; Development; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Hallucinations; HLA-G; HLA-G Antigens - genetics; Humans; INDEL Mutation - genetics; Infection; Inflammation; Male; Middle Aged; Polymorphism, Genetic; Pregnancy; Risk; Schizophrenia; Schizophrenia - genetics; Young Adult; Untranslated Region; Insertion/Deletion; GWAS; FRS; Interleukin; Schizophrenia; MHC; Scale for the Assessment of Negative Symptoms; Maternal Immune Activation; bp; Mini International Neuropsychiatric Interview; INDEL; Scale for the Assessment of Positive Symptoms; UTR; Human Leukocyte Antigen; Transforming Growth Factor- β1; HWE; Development; Genome Wide Association Studies; DSM; Auditory Hallucinations; Diagnostic and Statistical Manual of Mental Disorders; First Rank Symptom; Major Histocompatibility Complex; IL; CGI; MIA; AH; Inflammation; Base Pair; HLA-G; Infection; Human Leukocyte Antigen–G; MINI; sHLA-G; SANS; SAPS; Soluble Human Leukocyte Antigen G; Hallucinations; TGF-β1; Clinical Global Impression; HLA; Hardy Weinberg Equilibrium
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2016.08.013

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 and 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 [14 bp 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.