Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia

A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sonal Saxena, Pranay Amruth Maroju, Sumana Choudhury, Vidhya Chitta Voina, Poonam Naik, Kavitha Gowdhaman, Poornima Kkani, Kiranmai Chennoju, S. Ganesh Kumar, C. Ramasubramanian, G. Prasad Rao, Trinath Jamma, Kumar Pranav Narayan, K. Naga Mohan
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi - Cambridge University Press 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/28798b94df534441895eee949185e1f1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:28798b94df534441895eee949185e1f1
record_format	dspace
spelling	oai:doaj.org-article:28798b94df534441895eee949185e1f12021-12-02T17:48:24ZFunctional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia0016-67231469-507310.1155/2021/6698979https://doaj.org/article/28798b94df534441895eee949185e1f12021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6698979https://doaj.org/toc/0016-6723https://doaj.org/toc/1469-5073A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ (P = 0.04 for rs2114724 and P = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered (P ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females (P = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T (P = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.Sonal SaxenaPranay Amruth MarojuSumana ChoudhuryVidhya Chitta VoinaPoonam NaikKavitha GowdhamanPoornima KkaniKiranmai ChennojuS. Ganesh KumarC. RamasubramanianG. Prasad RaoTrinath JammaKumar Pranav NarayanK. Naga MohanHindawi - Cambridge University PressarticleGeneticsQH426-470ENGenetics Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Sonal Saxena Pranay Amruth Maroju Sumana Choudhury Vidhya Chitta Voina Poonam Naik Kavitha Gowdhaman Poornima Kkani Kiranmai Chennoju S. Ganesh Kumar C. Ramasubramanian G. Prasad Rao Trinath Jamma Kumar Pranav Narayan K. Naga Mohan Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
description	A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ (P = 0.04 for rs2114724 and P = 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered (P ≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females (P = 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T (P = 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.
format	article
author	Sonal Saxena Pranay Amruth Maroju Sumana Choudhury Vidhya Chitta Voina Poonam Naik Kavitha Gowdhaman Poornima Kkani Kiranmai Chennoju S. Ganesh Kumar C. Ramasubramanian G. Prasad Rao Trinath Jamma Kumar Pranav Narayan K. Naga Mohan
author_facet	Sonal Saxena Pranay Amruth Maroju Sumana Choudhury Vidhya Chitta Voina Poonam Naik Kavitha Gowdhaman Poornima Kkani Kiranmai Chennoju S. Ganesh Kumar C. Ramasubramanian G. Prasad Rao Trinath Jamma Kumar Pranav Narayan K. Naga Mohan
author_sort	Sonal Saxena
title	Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
title_short	Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
title_full	Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
title_fullStr	Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
title_full_unstemmed	Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
title_sort	functional analysis of dnmt1 snps (rs2228611 and rs2114724) associated with schizophrenia
publisher	Hindawi - Cambridge University Press
publishDate	2021
url	https://doaj.org/article/28798b94df534441895eee949185e1f1
work_keys_str_mv	AT sonalsaxena functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT pranayamruthmaroju functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT sumanachoudhury functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT vidhyachittavoina functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT poonamnaik functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT kavithagowdhaman functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT poornimakkani functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT kiranmaichennoju functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT sganeshkumar functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT cramasubramanian functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT gprasadrao functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT trinathjamma functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT kumarpranavnarayan functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia AT knagamohan functionalanalysisofdnmt1snpsrs2228611andrs2114724associatedwithschizophrenia
_version_	1718379454596644864

Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia

Ejemplares similares