Cargando…
DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia
DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in p...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032286/ https://www.ncbi.nlm.nih.gov/pubmed/24859147 http://dx.doi.org/10.1371/journal.pone.0098182 |
_version_ | 1782317623817535488 |
---|---|
author | Saradalekshmi, Koramannil Radha Neetha, Nanoth Vellichiramal Sathyan, Sanish Nair, Indu V. Nair, Chandrasekharan M. Banerjee, Moinak |
author_facet | Saradalekshmi, Koramannil Radha Neetha, Nanoth Vellichiramal Sathyan, Sanish Nair, Indu V. Nair, Chandrasekharan M. Banerjee, Moinak |
author_sort | Saradalekshmi, Koramannil Radha |
collection | PubMed |
description | DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022) were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023) and allele (P = 0.0063) increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia. |
format | Online Article Text |
id | pubmed-4032286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40322862014-05-28 DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia Saradalekshmi, Koramannil Radha Neetha, Nanoth Vellichiramal Sathyan, Sanish Nair, Indu V. Nair, Chandrasekharan M. Banerjee, Moinak PLoS One Research Article DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022) were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023) and allele (P = 0.0063) increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia. Public Library of Science 2014-05-23 /pmc/articles/PMC4032286/ /pubmed/24859147 http://dx.doi.org/10.1371/journal.pone.0098182 Text en © 2014 Saradalekshmi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Saradalekshmi, Koramannil Radha Neetha, Nanoth Vellichiramal Sathyan, Sanish Nair, Indu V. Nair, Chandrasekharan M. Banerjee, Moinak DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title | DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title_full | DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title_fullStr | DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title_full_unstemmed | DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title_short | DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia |
title_sort | dna methyl transferase (dnmt) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032286/ https://www.ncbi.nlm.nih.gov/pubmed/24859147 http://dx.doi.org/10.1371/journal.pone.0098182 |
work_keys_str_mv | AT saradalekshmikoramannilradha dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT neethananothvellichiramal dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT sathyansanish dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT nairinduv dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT nairchandrasekharanm dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT banerjeemoinak dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia |