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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4032286?pdf=render |
| _version_ | 1818858393033506816 |
|---|---|
| author | Koramannil Radha Saradalekshmi Nanoth Vellichiramal Neetha Sanish Sathyan Indu V Nair Chandrasekharan M Nair Moinak Banerjee |
| author_facet | Koramannil Radha Saradalekshmi Nanoth Vellichiramal Neetha Sanish Sathyan Indu V Nair Chandrasekharan M Nair Moinak Banerjee |
| author_sort | Koramannil Radha Saradalekshmi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:55:34Z |
| format | Article |
| id | doaj.art-7617ee71a7d94df19e732a1971ef7bdb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T08:55:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7617ee71a7d94df19e732a1971ef7bdb2022-12-21T20:28:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9818210.1371/journal.pone.0098182DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia.Koramannil Radha SaradalekshmiNanoth Vellichiramal NeethaSanish SathyanIndu V NairChandrasekharan M NairMoinak BanerjeeDNA 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.http://europepmc.org/articles/PMC4032286?pdf=render |
| spellingShingle | Koramannil Radha Saradalekshmi Nanoth Vellichiramal Neetha Sanish Sathyan Indu V Nair Chandrasekharan M Nair Moinak Banerjee DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4032286?pdf=render |
| work_keys_str_mv | AT koramannilradhasaradalekshmi dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT nanothvellichiramalneetha dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT sanishsathyan dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT induvnair dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT chandrasekharanmnair dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia AT moinakbanerjee dnamethyltransferasednmtgenepolymorphismscouldbeaprimaryeventinepigeneticsusceptibilitytoschizophrenia |