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Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis
SIMPLE SUMMARY: Even though in monogenic diseases a mutation will lead to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495465/ https://www.ncbi.nlm.nih.gov/pubmed/36138766 http://dx.doi.org/10.3390/biology11091287 |
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author | Ruiz Ramírez, Andrea Virginia Prado Montes de Oca, Ernesto Figuera, Luis E |
author_facet | Ruiz Ramírez, Andrea Virginia Prado Montes de Oca, Ernesto Figuera, Luis E |
author_sort | Ruiz Ramírez, Andrea Virginia |
collection | PubMed |
description | SIMPLE SUMMARY: Even though in monogenic diseases a mutation will lead to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could be modifying the phenotype of FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (cardiac myocytes, cardiac fibroblasts, astrocytes-cerebellar, endothelial cells and T helper cells 1-T(H)1). Each SNP was confirmed as a true rSNP in public eQTL databases and prediction of variants was suggested by additional software. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The rSNPs described here could act to modulate Fabry’s clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered genetic modifiers in FD. ABSTRACT: Even though a mutation in monogenic diseases leads to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could modify the FD phenotype FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (Cardiac myocytes and fibroblasts, Astrocytes-cerebellar, endothelial cells and T helper cells 1-T(H)1). Each SNP was confirmed as a true rSNP in public eQTL databases, and additional software suggested the prediction of variants. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The seven rSNPs described here could act to modulate Fabry’s clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered minor genes in FD. |
format | Online Article Text |
id | pubmed-9495465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94954652022-09-23 Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis Ruiz Ramírez, Andrea Virginia Prado Montes de Oca, Ernesto Figuera, Luis E Biology (Basel) Article SIMPLE SUMMARY: Even though in monogenic diseases a mutation will lead to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could be modifying the phenotype of FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (cardiac myocytes, cardiac fibroblasts, astrocytes-cerebellar, endothelial cells and T helper cells 1-T(H)1). Each SNP was confirmed as a true rSNP in public eQTL databases and prediction of variants was suggested by additional software. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The rSNPs described here could act to modulate Fabry’s clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered genetic modifiers in FD. ABSTRACT: Even though a mutation in monogenic diseases leads to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could modify the FD phenotype FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (Cardiac myocytes and fibroblasts, Astrocytes-cerebellar, endothelial cells and T helper cells 1-T(H)1). Each SNP was confirmed as a true rSNP in public eQTL databases, and additional software suggested the prediction of variants. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The seven rSNPs described here could act to modulate Fabry’s clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered minor genes in FD. MDPI 2022-08-30 /pmc/articles/PMC9495465/ /pubmed/36138766 http://dx.doi.org/10.3390/biology11091287 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ruiz Ramírez, Andrea Virginia Prado Montes de Oca, Ernesto Figuera, Luis E Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title | Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title_full | Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title_fullStr | Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title_full_unstemmed | Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title_short | Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis |
title_sort | prediction of regulatory snps in putative minor genes of the neuro-cardiovascular variant in fabry reveals insights into autophagy/apoptosis and fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495465/ https://www.ncbi.nlm.nih.gov/pubmed/36138766 http://dx.doi.org/10.3390/biology11091287 |
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