title: The impact of IL10 polymorphisms and sHLA-G levels on the risk of schizophrenia.
abstract: Early life immune aberrations have strongly been associated with the risk of schizophrenia. Amongst them, inflammation induced neurodevelopmental origin has emerged as one of the widely recognized underlying mechanisms. Interleukin-10 (IL-10) is an important anti-inflammatory and immunoregulatory cytokine. It modulates the expression of another immuno-inhibitory molecule, Human Leukocyte Antigen-G (HLA-G), predominantly expressed at the feto-maternal interface. Under physiological conditions, IL-10 and HLA-G molecules regulate the feto-maternal immune homeostasis by limiting the inflammatory states and influence the outcome of pregnancy. The aberrant expression of these molecules can cause pregnancy complications, which are known to confer strong risk to schizophrenia in the offspring. However, there is a considerable lack of information on the effect of the functional interactions between IL-10 and HLA-G on the risk of schizophrenia. We therefore examined the impact of possible correlation between IL-10 genetic variations and the plasma levels of soluble HLA-G (sHLA-G) on schizophrenia risk. Genotyping of IL10 (-592 C>A, -1082 A>G) single nucleotide polymorphisms (SNPs) was performed by PCR-RFLP method in 219 schizophrenia patients and 197 healthy subjects and levels of sHLA-G were estimated by ELISA in 46 patients and 44 healthy subjects. There was no significant difference in the genotype and allele frequencies between the groups for both the IL10 SNPs analyzed. However, we observed a correlation between IL10 genetic variation and plasma levels of sHLA-G in schizophrenia patients. Patients carrying CC genotype of IL10 -592C>A polymorphism had significantly lower sHLA-G levels compared to CA and AA genotypes. Our findings suggest the impact of possible correlation between IL-10 and HLA-G on schizophrenia risk.
authors.affiliation: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Rajasekaran
authors.affiliation: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Venkataram
authors.initials: V
authors.lastname: Shivakumar
authors.affiliation: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Kalmady
authors.affiliation: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Janardhanan C
authors.initials: JC
authors.lastname: Narayanaswamy
authors.affiliation: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Subbana
authors.affiliation: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Venugopal
authors.affiliation: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Anekal C
authors.initials: AC
authors.lastname: Amaresha
authors.affiliation: Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address: monozeet@gmail.com.
authors.forename: Monojit
authors.initials: M
authors.lastname: Debnath
mesh_terms: D000328:Adult; D005260:Female; D059951:HLA-G Antigens / Q000097:blood*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics*
chemical_list: D059951:HLA-G Antigens; C508609:IL10 protein, human; D016753:Interleukin-10
keywords: HLA-G; IL-10; Inflammation; Neurodevelopment; Schizophrenia