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Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population
The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530687/ https://www.ncbi.nlm.nih.gov/pubmed/37761945 http://dx.doi.org/10.3390/genes14091805 |
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author | Kolb, Kathleen Liedtke Mira, Ana Luiza Sprotte Auer, Eduardo Delabio Bucco, Isabela Dall’Oglio de Lima e Silva, Carla Eduarda dos Santos, Priscila Ianzen Hoch, Valéria Bumiller-Bini Oliveira, Luana Caroline Hauser, Aline Borsato Hundt, Jennifer Elisabeth Shuldiner, Alan R. Lopes, Fabiana Leão Boysen, Teide-Jens Franke, Andre Pinto, Luis Felipe Ribeiro Soares-Lima, Sheila Coelho Kretzschmar, Gabriela Canalli Boldt, Angelica Beate Winter |
author_facet | Kolb, Kathleen Liedtke Mira, Ana Luiza Sprotte Auer, Eduardo Delabio Bucco, Isabela Dall’Oglio de Lima e Silva, Carla Eduarda dos Santos, Priscila Ianzen Hoch, Valéria Bumiller-Bini Oliveira, Luana Caroline Hauser, Aline Borsato Hundt, Jennifer Elisabeth Shuldiner, Alan R. Lopes, Fabiana Leão Boysen, Teide-Jens Franke, Andre Pinto, Luis Felipe Ribeiro Soares-Lima, Sheila Coelho Kretzschmar, Gabriela Canalli Boldt, Angelica Beate Winter |
author_sort | Kolb, Kathleen Liedtke |
collection | PubMed |
description | The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression. |
format | Online Article Text |
id | pubmed-10530687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105306872023-09-28 Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population Kolb, Kathleen Liedtke Mira, Ana Luiza Sprotte Auer, Eduardo Delabio Bucco, Isabela Dall’Oglio de Lima e Silva, Carla Eduarda dos Santos, Priscila Ianzen Hoch, Valéria Bumiller-Bini Oliveira, Luana Caroline Hauser, Aline Borsato Hundt, Jennifer Elisabeth Shuldiner, Alan R. Lopes, Fabiana Leão Boysen, Teide-Jens Franke, Andre Pinto, Luis Felipe Ribeiro Soares-Lima, Sheila Coelho Kretzschmar, Gabriela Canalli Boldt, Angelica Beate Winter Genes (Basel) Article The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression. MDPI 2023-09-15 /pmc/articles/PMC10530687/ /pubmed/37761945 http://dx.doi.org/10.3390/genes14091805 Text en © 2023 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 Kolb, Kathleen Liedtke Mira, Ana Luiza Sprotte Auer, Eduardo Delabio Bucco, Isabela Dall’Oglio de Lima e Silva, Carla Eduarda dos Santos, Priscila Ianzen Hoch, Valéria Bumiller-Bini Oliveira, Luana Caroline Hauser, Aline Borsato Hundt, Jennifer Elisabeth Shuldiner, Alan R. Lopes, Fabiana Leão Boysen, Teide-Jens Franke, Andre Pinto, Luis Felipe Ribeiro Soares-Lima, Sheila Coelho Kretzschmar, Gabriela Canalli Boldt, Angelica Beate Winter Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title_full | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title_fullStr | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title_full_unstemmed | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title_short | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
title_sort | glucocorticoid receptor gene (nr3c1) polymorphisms and metabolic syndrome: insights from the mennonite population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530687/ https://www.ncbi.nlm.nih.gov/pubmed/37761945 http://dx.doi.org/10.3390/genes14091805 |
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